The homologous recombination (HR) repair pathway for DNA damage, particularly the BRCA1 and BRCA2 genes, has become a target for cancer therapy, with poly ADP-ribose polymerase (PARP) inhibitors ...showing significant outcomes in treating germline BRCA1/2 (gBRCA1/2) mutated breast cancer. Recent studies suggest that some patients with somatic BRCA1/2 (sBRCA1/2) mutation or mutations in HR-related genes other than BRCA1/2 may benefit from PARP inhibitors as well, particularly those with PALB2 mutations. The current analysis aims to evaluate the prevalence of genetic alterations specific to BRCA1, BRCA2, and PALB2 in a large cohort of Taiwanese breast cancer patients through tumor-targeted sequencing.
A total of 924 consecutive assays from 879 Taiwanese breast cancer patients underwent tumor-targeted sequencing (Thermo Fisher Oncomine Comprehensive Assay v3). We evaluated BRCA1, BRCA2, and PALB2 mutational profiles, with variants annotated and curated by the ClinVAR, the Oncomine™ Knowledgebase Reporter, and the OncoKB™. We also conducted reflex germline testing using either whole exome sequencing (WES) or whole genome sequencing (WGS), which is ongoing.
Among the 879 patients analyzed (924 assays), 130 had positive mutations in BRCA1 (3.1%), BRCA2 (8.6%), and PALB2 (5.2%), with a total of 14.8% having genetic alterations. Co-occurrence was noted between BRCA1/BRCA2, BRCA1/PALB2, and BRCA2/PALB2 mutations. In BRCA1-mutated samples, only p.K654fs was observed in three patients, while other variants were observed no more than twice. For BRCA2, p.N372H was the most common (26 patients), followed by p.S2186fs, p.V2466A, and p.X159_splice (5 times each). For PALB2, p.I887fs was the most common mutation (30 patients). This study identified 176 amino acid changes; 60.2% (106) were not documented in either ClinVAR or the Oncomine™ Knowledgebase Reporter. Using the OncoKB™ for annotation, 171 (97.2%) were found to have clinical implications. For the result of reflex germline testing, three variants (BRCA1 c.1969_1970del, BRCA1 c.3629_3630del, BRCA2 c.8755-1G > C) were annotated as Pathogenic/Likely pathogenic (P/LP) variants by ClinVar and as likely loss-of-function or likely oncogenic by OncoKB; while one variant (PALB2 c.448C > T) was not found in ClinVar but was annotated as likely loss-of-function or likely oncogenic by OncoKB.
Our study depicted the mutational patterns of BRCA1, BRCA2, and PALB2 in Taiwanese breast cancer patients through tumor-only sequencing. This highlights the growing importance of BRCA1/2 and PALB2 alterations in breast cancer susceptibility risk and the treatment of index patients. We also emphasized the need to meticulously annotate variants in cancer-driver genes as well as actionable mutations across multiple databases.
Some organic dyes and photosensitizers with strong visible absorption can behave as photo-responsive oxidase mimics. However, the relationship between the photo-oxidase activity and molecular ...structure remains unclear to date. In this work, a new type of photosensitizer with the characteristics of molecular rotors, namely DPPy, served as the molecular scaffold for further investigation. To adjust the photocatalytic oxidation ability, DAPy and CBPy were designed and synthesized based on the enhancement and diminishment of the intramolecular charge transfer (ICT) process, respectively. Kinetic studies revealed that DAPy and CBPy both exhibited highly efficient photo-activated oxidase-like activity with 3,3',5,5'-tetramethylbenzidine (TMB) as the substrate, which were in good accordance with their molecular engineering to promote either type I or type II reactive oxygen species (ROS) generation. Impressively a colorimetric method based on the visible light induced oxidase-like activity of molecular rotors was developed to determine the environmental temperature for the first time. Both DAPy and CBPy showed distinct sensitivities toward temperature as compared with several molecular rotors based on the typical fluorimetric detection. This work provides a new strategy for the application of molecular rotors to overcome the non-emissive challenge in temperature sensing.
Chronic kidney disease has been linked to cognitive impairment and morphological brain change. However, less is known about the impact of kidney functions on cerebral cortical thickness. This study ...investigated the relationship between kidney functions and global or lobar cerebral cortical thickness (CTh) in 259 non-demented elderly persons. Forty-three participants (16.7%) had kidney dysfunction, which was defined as either a glomerular filtration rate (GFR) of <60 ml/min/1.73 m
or presence of proteinuria. Kidney dysfunction was associated with lower global (β = -0.05, 95% CI = -0.08 to -0.01) as well as frontal, parietal, temporal, occipital, and insular lobar CTh. In the stratified analysis, the associations were more pronounced in women, APOEε4 non-carriers, and participants with a lower cognitive score. Besides, kidney dysfunction significantly increased the risk of cortical thinning, defined as being the lowest CTh tertile, in the insular lobe (adjusted odds ratio = 2.74, 95% CI = 1.31-5.74). Our results suggested that kidney dysfunction should be closely monitored and managed in elderly population to prevent neurodegeneration.
With the rapid growth in global energy consumption, the recovery of waste heat is becoming an important issue. Nevertheless, the recovery of near-room-temperature waste heat remains challenging ...because the slight temperature difference with the surroundings leads to extremely low thermoelectric power generation. In this study, we combined a daytime radiative cooling (DRC) technology with a thermoelectric generator (TEG) to efficiently recover near-room-temperature waste heat. We investigated the effects of the thermal radiation and thermal conduction properties of DRC materials on near-room-temperature waste heat recovery (WHR). We designed a hierarchical micro-nano h-BN/ZnO composite (MNHZC) that possessed an outstanding daytime radiative cooling ability and moderate thermal conductivity. With this hierarchical h-BN/ZnO composite, we achieved record-high levels of thermoelectric power generation of 225.3 and 412.3 mW m
−2
during the daytime and nighttime, respectively, with enhancements in thermoelectric power of 1030 and 190%, respectively. The attractive power generation ability of the MNHZC/TEG system suggests its great potential in low-grade waste heat recovery and environmental energy harvesting by consistently generating power in both the daytime and nighttime.
A newly designed daytime radiative cooling (DRC) strategy significantly enhances near-room-temperature waste heat recovery, generating power in both the daytime and nighttime.
Correct quantification of transcript expression is essential to understand the functional elements in different physiological conditions. For the organisms without the reference transcriptome, de ...novo transcriptome assembly must be carried out prior to quantification. However, a large number of erroneous contigs produced by the assemblers might result in unreliable estimation. In this regard, this study investigates how assembly quality affects the performance of quantification based on de novo transcriptome assembly. We examined the over-extended and incomplete contigs, and demonstrated that assembly completeness has a strong impact on the estimation of contig abundance. Then we investigated the behavior of the quantifiers with respect to sequence ambiguity which might be originally presented in the transcriptome or accidentally produced by assemblers. The results suggested that the quantifiers often over-estimate the expression of family-collapse contigs and under-estimate the expression of duplicated contigs. For organisms without reference transcriptome, it remains challenging to detect the inaccurate estimation on family-collapse contigs. On the contrary, we observed that the situation of under-estimation on duplicated contigs can be warned through analyzing the read proportion of estimated abundance (RPEA) of contigs in the connected component inferenced by the quantifiers. In addition, we suggest that the estimated quantification results on the connected component level have better accuracy over sequence level quantification. The analytic results conducted in this study provides valuable insights for future development of transcriptome assembly and quantification.
Emerging infectious diseases (EIDs), including the latest COVID-19 pandemic, have emerged and raised global public health crises in recent decades. Without existing protective immunity, an EID may ...spread rapidly and cause mass casualties in a very short time. Therefore, it is imperative to identify cases with risk of disease progression for the optimized allocation of medical resources in case medical facilities are overwhelmed with a flood of patients. This study has aimed to cope with this challenge from the aspect of preventive medicine by exploiting machine learning technologies. The study has been based on 83,227 hospital admissions with influenza-like illness and we analysed the risk effects of 19 comorbidities along with age and gender for severe illness or mortality risk. The experimental results revealed that the decision rules derived from the machine learning based prediction models can provide valuable guidelines for the healthcare policy makers to develop an effective vaccination strategy. Furthermore, in case the healthcare facilities are overwhelmed by patients with EID, which frequently occurred in the recent COVID-19 pandemic, the frontline physicians can incorporate the proposed prediction models to triage patients suffering minor symptoms without laboratory tests, which may become scarce during an EID disaster. In conclusion, our study has demonstrated an effective approach to exploit machine learning technologies to cope with the challenges faced during the outbreak of an EID.
Plasmonics have been well investigated on photodetectors, particularly in IR and visible regimes. However, for a wide range of ultraviolet (UV) applications, plasmonics remain unavailable mainly ...because of the constrained optical properties of applicable plasmonic materials in the UV regime. Therefore, an epitaxial single‐crystalline aluminum (Al) film, an abundant metal with high plasma frequency and low intrinsic loss is fabricated, on a wide bandgap semiconductive gallium nitride (GaN) to form a UV photodetector. By deliberately designing a periodic nanohole array in this Al film, localized surface plasmon resonance and extraordinary transmission are enabled; hence, the maximum responsivity (670 A W−1) and highest detectivity (1.48 × 1015 cm Hz1/2 W−1) is obtained at the resonance wavelength of 355 nm. In addition, owing to coupling among nanoholes, the bandwidth expands substantially, encompassing the entire UV range. Finally, a Schottky contact is formed between the single‐crystalline Al nanohole array and the GaN substrate, resulting in a fast temporal response with a rise time of 51 ms and a fall time of 197 ms. To the best knowledge, the presented detectivity is the highest compared with those of other reported GaN photodetectors.
Aluminum plasmonics is merged as an advancement tool to boost GaN a superior complementary metal oxide semiconductor (CMOS) compatible UV photodetector. By introducing a single‐crystalline Al nanohole array on a GaN substrate, it enables ultraviolet plasmons and Schottky barrier, and thus demonstrates excellent performance in entire UV regime: maximum responsivity (670 A W−1), highest detectivity (1.48 × 1015 cm Hz1/2 W−1), and fast temporal response.
Control of the orientation, diameter, and length of silicon nanowires (SiNWs) is achieved in large‐scale single‐crystalline SiNW arrays fabricated by a statistical electroless metal deposition ...technique. Taguchi methods are employed to optimize the diameter control and to understand the influence of all processing factors on the growth. The 〈100〉 directions are found to be the preferred crystallographic orientation of the growing SiNWs (see figure).
Objective
Cerebral cavernous malformations (CCMs) present variably, and epileptic seizures are the most common symptom. The factors contributing to cavernoma‐related epilepsy (CRE) and drug ...resistance remain inconclusive. The outcomes of CRE after different treatment modalities have not yet been fully addressed. This study aimed to characterize the clinical features of patients with CRE and the long‐term seizure outcomes of medical and surgical treatment strategies.
Methods
This was a retrospective cohort of 135 patients with CCM who were diagnosed in 2007–2011 and followed up for 93.6 months on average. The patients were divided into drug‐resistant epilepsy (DRE; n = 29), non‐DRE (n = 45), and no epilepsy (NE; n = 61).
Results
Temporal CCM was the factor most strongly associated with the development of both CRE and DRE. The majority of patients with single temporal CCMs had CRE (86.8%, n = 33), and 50% had DRE, whereas only 14.7% (n = 5) with a nontemporal supratentorial CCM had DRE (p < .05). The most common lesion site in the DRE group was the mesiotemporal lobe (50%). Multiple CCMs were more frequently observed in the CRE (29.2%) than the NE (11.5%) group (p < .05). In patients with CRE, multiple lesions were associated with a higher rebleeding rate (odds ratio = 11.1), particularly in those with DRE (odds ratio = 15.4). The majority of patients who underwent resective surgery for DRE (76.5%, n = 13) achieved International League Against Epilepsy Class I and II seizure outcomes even after a long disease course.
Significance
Temporal CCM not only predisposes to CRE but also is a major risk factor for drug resistance. The mesiotemporal lobe is the most epileptogenic zone. Multiple CCMs are another risk factor for CRE and increase the rebleeding risk in these patients. Surgical resection could provide beneficial long‐term seizure outcomes in patients with DRE.
Background & Aims: Following the world’s first successful implementation of a universal hepatitis B virus (HBV) vaccination program for infants in Taiwan 20 years ago, we performed this study to ...evaluate the long-term protection afforded by HBV vaccination and to rationalize further prevention strategies. Methods: HBV seromarkers, including hepatitis B surface antigen (HBsAg) and antibodies to HBsAg (anti-HBs) and core antigen (anti-HBc), were studied in 18,779 subjects from neonates to adults below 30 years of age in 2004. The birth cohort effect was evaluated by comparing the results of the same birth cohorts at different ages among this survey and the previous 1984, 1989, 1994, and 1999 surveys. Results: The seropositive rates for HBsAg, anti-HBs, and anti-HBc were 1.2%, 50.5%, and 3.7%, respectively, in those born after the vaccination program (<20 years of age) in 2004. A positive maternal HBsAg status was found in 89% of the HBsAg seropositive subjects born after the vaccination program. The absence of an increase in HBsAg seropositive subjects at different ages in the same birth cohorts born after the vaccination program implied no increased risk of persistent HBV infection with aging. Conclusions: Universal HBV vaccination provides long-term protection up to 20 years, and a universal booster is not indicated for the primary HBV vaccinees before adulthood. Maternal transmission is the primary reason for vaccine failure and is the challenge that needs to be addressed in future vaccination programs. This may include an appropriate hepatitis B immunoglobulin administration strategy for high-risk infants and involve efforts to minimize noncompliance.
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