bluuebunny/crossref_metadata_2025 huggingface dataset:
Confirming Putative Variants at ≤5% Allele Frequency Using Allele Enrichment and Sanger Sequencing
Authors: Yan Yan Helen , Chen Sherry X. , Cheng Lauren Y. , Rodriguez Alyssa Y. , Tang Rui , Cabrera Karina , Zhang David Yu
Published: February 2021

Whole exome sequencing (WES) is used to identify mutations in a patient’s tumor DNA that are predictive of tumor behavior, including the likelihood of response or resistance to cancer therapy. WES has a mutation limit of detection (LoD) at variant allele frequencies (VAF) of 5%. Putative mutations called at ≤5% VAF are frequently due to sequencing errors, therefore reporting these subclonal mutations incurs risk of significant false positives. Here we performed ~1000x WES on fresh-frozen and formalin-fixed paraffin-embedded (FFPE) tissue biopsy samples from a non-small cell lung cancer patient, and identified 226 putative mutations at between 0.5% and 5% VAF. Each variant was then tested using NuProbe NGSureTM, to confirm the original WES calls. NGSure utilizes Blocker Displacement Amplification to first enrich the allelic fraction of the mutation and then uses Sanger sequencing to determine mutation identity. Results showed that 52% of the 226 (117) putative variants were disconfirmed, among which 2% (5) putative variants were found to be misidentified in WES. In the 66 cancer-related variants, the disconfirmed rate was 82% (54/66). This data demonstrates Blocker Displacement Amplification allelic enrichment coupled with Sanger sequencing can be used to confirm putative mutations ≤5% VAF. By implementing this method, next-generation sequencing can reliably report low-level variants at a high sensitivity, without the cost of high sequencing depth.
Community Health Workers’ Augment The Cascade of TB Detection To Care In Urban Slums of Two Metro Cities In India
Authors: Potty Rajaram Subramanian , K Karthikeyan , A Rajesham , Reddy Ramesh Chandra , Singarajipura Anil , Siddappa Poornima Bathi , BS Prarthana , T Raghavendra , HL Mohan , Swamickan Reuben , Shah Amar , Panibatla Vikas , Dasari Ramesh , Washington Reynold
Published: February 2021

Background:Tuberculosis Health Action Learning Initiative (THALI) funded by USAID is a person-centered initiative, supporting vulnerable urban populations to gain access to TB services. THALI trained and placed 112 Community health workers (CHWs) to detect and support individuals with TB symptoms or disease within urban slums in two cities, Hyderabad and Bengaluru, covering a population of about 3 Million. Method: CHWs visited the slums once in a fortnight. They conducted TB awareness activities. They referred individuals with TB symptoms for sputum testing to nearest public sector labs. They visited those testing TB positive, once a fortnight in the intensive phase, and once a month thereafter. They supported TB patients and families with counselling, contact screening and social scheme linkages. They complemented the shortfall in urban TB government field staff numbers and their capacity to engage with TB patients. Data on CHWs’ patient referral for TB diagnosis and treatment support activities was entered into a data-base and analyzed to examine CHWs’ role in the cascade of TB care. We compared achievements of six monthly referral cohorts from September 2016 to February 2019.Results:Overall, 31617 (approximately 1%) of slum population were identified as TB symptomatic and referred for diagnosis. Among the referred persons, 23976 (76%) underwent testing of which 3841 (16%) were TB positive. Overall, 3812 (99%) were initiated on treatment and 2760(72%) agreed for regular followed up by CHWs. Fifty-seven percent of 2952 referred were tested in the first cohort, against 86% of 8315 in the last cohort. The annualized case detection rate through CHW referrals in Bengaluru increased from 5.5 to 52.0 per 100000 during the period, while in Hyderabad it was 35.4 initially and increased up to 118.9 per 100000 persons. The treatment success rate was 87.1% among 193 in the first cohort versus 91.3% among 677 in the last cohort. Conclusions CHWs in urban slums augment TB detection to care cascade. Their performance and TB treatment outcomes improve over time. It would be important to examine the cost per TB case detected and successfully treated.
The use of Fretsaw as a Substitute Osteotomy Tool while Oscillating Saw Malfunction in Hip Arthroplasty
Authors: Zhai Zanjing , Chang Yongyun , Yu Degang , Li Huiwu , Mao Yuanqing , Zeng Yiming , Yan Mengning
Published: February 2021

Background: The occurrence of oscillating saw malfunction, power shortage, or contamination occurs frequently when implementing femoral neck osteotomy during total hip arthroplasty (THA). This study aimed to introduce the fretsaw as a novel substitute osteotomy tool with various advantages.Methods: Twenty patients (20 hips) who underwent primary THA were included. Ten patients underwent femoral neck osteotomy using a fretsaw, while the other 10 patients underwent the procedure using an oscillating saw. Intraoperative evaluation and radiographic data were obtained for all patients during and after surgery.Results: The mean osteotomy time was 20.60 ± 1.08s (range 16–27) and 22.10 ± 1.49s (range 16–31) in the oscillating saw and fretsaw groups, respectively. The mean osteotomy height was 1.21 ± 0.16 (range 1.01–1.43) cm and 1.14 ± 0.08 (range 1.02–1.28) cm in the oscillating saw and fretsaw groups, respectively. The use of fretsaw did not result in bone notch or blood splashes.Conclusion: The fretsaw can be a substitute femoral neck osteotomy tool with various advantages in THA while oscillating saw malfunction.
Changes in UPR-PERK pathway and muscle hypertrophy following resistance training and creatine supplementation in rats
Authors: Nouri Hersh , Sheikholeslami-Vatani Dariush , Moloudi Mohammad Raman
Published: February 2021

The unfolded protein response (UPR) plays a pivotal role in some exercise training induced-physiological adaptation. Our aim was to evaluate the changes in the protein kinase R-like endoplasmic reticulum kinase (PERK) arm of the UPR and hypertrophy signaling pathway following 8 weeks of resistance training and creatine (Cr) supplementation in rats. Thirty-two adult male Wistar rats (8 weeks old) were randomly divided into 4 groups of 8: untrained + placebo (UN + P), resistance training + placebo (RT + P), untrained + Cr (UN + Cr) and resistance training + Cr (RT + Cr). Trained animals were submitted to the ladder-climbing exercise training 5 days per week for a total of 8 weeks. Cr supplementation groups received creatine diluted with 1.5 ml of 5% dextrose orally. The flexor hallucis longus (FHL) muscle was extracted 48 hours after the last training session and used for western blotting. After training period, the RT + Cr and RT + P groups presented a significant increase in phosphorylated and phosphorylated /total ratio hypertrophy indices, phosphorylated and phosphorylated/total ratio PERK pathway proteins and other downstream proteins of the PERK cascade compared with their untrained counterparts (P < 0.05). The increase in hypertrophy indices were higher but PERK pathway proteins were lower in the RT-Cr group than in the RT + P group (P < 0.05). There was no significant difference between the untrained groups (P > 0.05). Our study suggests that resistance training in addition to Cr supplementation modifies PERK pathway response and improves skeletal muscle hypertrophy.
Efficacy of Anastomosis Enhancing Suture in Laparoscopic Anterior Resection of Middle-Low Rectal Cancer: A Prospective Cohort Study
Authors: Chen Jin-Shui , Zang Jia , Wei Shu-Xun , Yan Wen-Tao , Zhou Hai-Yang , Ruan Can-Ping , Wang Wei-Jun , Wang Yi , Sun Yan-Ping , Zhang Jian , Hu Zhi-Qian
Published: February 2021

Background：Anastomotic leakage (AL) limits the outcome after laparoscopic anterior resection (LAR) for middle-low rectal cancer. The study investigated the efficacy of laparoscopic anastomosis enhancing suture (LAES), preventive ileostomy and transanal drainage tube placement in reducing anastomotic leakage after LAR for middle-low rectal cancer.Methods：From April 2016 to April 2019, a prospective cohort study was performed on consecutive patients who underwent LAR for middle-low rectal cancer in Changzheng hospital. The patients were divided into group A, B, C and D in which LAES, transanal drainage tube placement, protective ileostomy, and no preventive treatment were applied, respectively. Clinical characteristics, operative variables and postoperative complication were compared between the groups.Results：Among 320 patients, 24 (7.5%) developed AL and incidence rate of AL was 1.3%, 12.5%, 1.3% and 15.0% in the four groups, respectively. Left colic artery preservation and neoadjuvant chemotherapy were found not associated with the incidence of AL. A total of 0, 2, 2 and 5 patients had anastomotic bleeding in the four groups, respectively. No patient underwent reoperation in group A and group C, while 5.0% (4/80) of the patients had reoperation in group B and group D due to grade C AL with severe symptoms.Conclusions：Compared with preventive ileostomy, LAES was effective in preventing AL after LAR for middle-low rectal cancer and relieving the complications of AL. The transanal drainage tube placement did not reduce the risk of AL.The study was retrospectively registered with the Chinese Clinical Trial Registry on 28th June 2016 (code: ChiCTR-IOR-17011777).
Awareness, Knowledge and Prevention Practices Related to Lassa Fever Among Residents of Rural Communities in Southwest Nigeria: Implications for Prevention and Control
Authors: Aromolaran Olukemi
Published: February 2021

Background: Lassa fever (LF) is a haemorrhagic illness caused by Lassa virus. The primary reservoir of the virus is the multimammate rat, Mastomys natalensis. More than 3,000 laboratory-confirmed cases of Lassa fever and over 800 deaths have been recorded in Nigeria. This could be attributed to poor rat control and poor sanitation especially in the rural communities where the rats are often found. Increasing awareness and health education about LF have been advocated for its prevention and control. This study investigated the level of awareness, knowledge and prevention practices related to LF among residents in rural communities within Iwo and Ayedire Local Government Areas, Osun State, southwest Nigeria sequel to an awareness campaign. Methods: Structured questionnaire was administered within rural communities in Iwo and Ayedire and 675 participants responded for the survey by a random sampling technique. Descriptive statistics, Chi-square test of association (p = < 0.05) and logistic regressions were used to determine associations between demographic variables, level of knowledge and prevention practices. Results: The average age range was 25-39 years, 365 (54.07%) were male, 270 (40%) were married, 199 (29.48%) had up to secondary school education and 536 (79.41%) have heard about LF before. Respondents in Iwo town were more aware of LF than respondent from Ayedire. Only 3 (0.44%) had good knowledge of the transmission and symptoms of the disease and 304 (45.04%) do not have effective means of preventing rats into their homes. About 296 (43.85%) will go to a hospital if symptoms occur, while 118 (17.48%) will do self-medication. Forty-four (6.52%) were aware of good prevention practices. Logistic regression analysis showed that respondents aged 25–39 years were significantly more aware of Lassa fever than other age groups. Educated and married respondents showed significant relationship with good prevention practices than those without education and were not married. Conclusions: Although, the awareness of LF among the respondents was high, only very few had good knowledge of the transmission and symptoms of the disease. Therefore, it is important for the people to be well informed about the disease and good prevention practices in order to curtail the spread.
Semi-quantitative Analysis of Adenosine Perfusion Magnetic Resonance Imaging Outperforms Visual Analysis in Identifying Fractional Flow Reserve-Altered Intermediate-grade Coronary Artery Stenosis: A Pilot Study
Authors: Ghekiere Olivier , Dacher Jean-Nicolas , Dewilde Willem , Cools Wilfried , Dendale Paul , Nchimi Alain
Published: February 2021

PurposeTo evaluate the diagnostic accuracy of semi-quantitative adenosine perfusion magnetic resonance imaging(MRI) to determine fractional flow reserve(FFR)≤0.80 intermediate-grade coronary stenoses as compared to visual analysis.Methods Forty-six patients (mean age 61±9 years;33 males) with 49 intermediate-grade stenoses underwent adenosine perfusion MRI and FFR measurement within 4 months between 2010 and 2013. Retrospective interpretation of all prospectively acquired data was performed. MRI was visually assessed by 2 experienced readers twice with one-year interval, the second time with the knowledge of the diseased artery. All myocardial enhancement maximal upslopes were evaluated distal to the coronary stenosis (=RISK) and in remote myocardium supplied by normal arteries (=REMOTE); stress subendocardial relative myocardial perfusion index (RMPI; RISK/REMOTE upslopes) was assessed in predicting FFR≤0.80 stenoses. Deep learning boosting models including all RISK and REMOTE upslopes were fitted to confirm the added value of accounting for perfusion changes in remote myocardium for FFR prediction. Results The average FFR value was 0.84±0.09 and 15/49 (31%) stenoses were FFR≤0.80. Both readers had moderate accuracy (range: 36/49(73%)-38/49(78%)) in predicting FFR≤0.80 stenoses, even with the knowledge of the stenosis location. At a cutoff value of 0.84, stress subendocardial RMPI had higher accuracy (43/49(88%)) than individual visual readings to predict FFR≤0.80 stenoses. The best FFR prediction using the boosting model occurred when accounting for REMOTE myocardial perfusion parameters, leading to diagnostic accuracy of 44/49(90%) for FFR≤0.80. Conclusion Semi-quantitative adenosine perfusion MRI accounting for stress perfusion in remote myocardium predicts FFR≤0.80 intermediate-grade coronary stenoses with a higher accuracy than individual visual analysis.
A Comparative Study of Perioperative and Survival Outcomes of Robot-Assisted Radical Cystectomy in Patients Over 80 and Under 80 Years Old
Authors: Xie Shangxun , Zhao Zihan , Feng Baofu , Zhang Shiwei , Zhang Gutian , Li Xiaogong , Guo Hongqian , Rong Yang
Published: February 2021

Background: Radical cystectomy (RC) is the standard treatment for bladder cancer, but the safety and efficacy of this treatment for elderly people need to be considered. We compare perioperative data and survival outcomes between elderly (≥80 years) and younger (＜80 years) patients undergoing robot-assisted radical cystectomy (RARC).Methods: We reviewed demographic, perioperative clinical and follow-up data of 190 consecutive patients with urothelial carcinoma of bladder who received RARC from M ay 2015 to December 2018 in Nanjing Drum Tower Hospital. The patients were divided into 2 groups by age: ≥80 years and ＜80 years. Perioperative outcomes were compared between 2 groups. Logistic regression method was used to analyze the factors that may affect preoperative complications. Cox regression model was employed to analyze the factors affecting 3-year overall survival (OS), recurrence-free survival (RFS), and cancer-specific survival (CSS).Results: Of the 190 patients, 44 (23.2%) were octogenarians. The elderly patients did not statistically differ from younger patients in most of the demographic, perioperative and pathological information. American Society of Anesthesiologists (ASA) score (p=0.045) and Charlson comorbidity index (CCI) (p=0.035) could predicted high-grade and any grade complications, respectively. Positive lymph node and pT≥3 were main factors affecting OS, RFS and CSS. ASA score (p=0.048) and CCI (p=0.003) could predicted OS and RFS, respectively. Elderly group had worse OS (p=0.007) and CSS (p=0.027) but similar RFS (p=0.147) compared with younger group.Conclusion: The elderly who received RARC had similar risk of perioperative complications and RFS compared with younger patients. RARC could be an alternative treatment for select octogenarians.
Self-managed Abortion as a Medico-legal Intervention in Ghana: a Systematic Review
Authors: Gbagbo Fred Yao , Morhe Renee Aku Sitsofe , Morhe Emmanuel Komla Senanu
Published: February 2021

BackgroundWe examined the potential of improving self-managed abortion as a medico-legal intervention of safely and effectively resolving unwanted pregnancies in Ghana.MethodsWe undertook a systematic literature review on self-managed or self-induced abortion within the context of Ghanaian laws. We searched for studies from Advanced PubMed Central and Google Scholar and repositories of Public Universities in Ghana. With search words of self-managed or self-induced abortion and Ghanaian law, we found 13,100 papers. The search was then narrowed to studies conducted between 2015-2020 of which 22 most related papers were selected with Six (6) from the Advanced Google Scholar search, 18 from PubMed and 1 unpublished postgraduate thesis from a public university library.ResultsDespite a liberal law that supported positive and quite well-decentralized service delivery policy, standards, and protocols development on abortion in Ghana, self-induced abortion remains criminalized. Nonetheless, the longstanding practice persists with no evidence of prosecution of the person(s) found violating the law within the period under review. The use of abortifacients procured from pharmacies and chemists that are not recognized abortion care providers has become the leading method of self-induced. Conclusion Despite criminalizing self-induced abortion, Ghana’s law on abortion is fairly liberal enough to permit the development of comprehensive abortion care policy, standards, and protocols that have a good potential of supporting improved self-managed abortion to reduce maternal morbidity and mortality in the country. Further studies are required for the exploration of ways of filling implementation gaps to harness the potentials of improving self-managed abortions in Ghana.
Morbidity and Mortality Rates of Boer and Central Highland Goats at Ataye Crossbreeding Program Research Site: Non-parametric Survival Analysis and Piecewise Exponential Model
Authors: Tesema Erdachew Yitagesu , Alemnew Enyiew
Published: February 2021

Non-parametric survival analysis and piecewise exponential model (PEM) was used to estimate prevalence and incidence of goat mortality, to identify major clinical causes of morbidity and mortality related disease, and to investigate animal and environmental related risk factors affecting goat mortality at Ataye boer goat breeding and evaluation research site. A total of 671 kids and 347 adult (yearling) age goats were used for the analysis of non-parametric survival and piecewise exponential model for survival, mortality incidence rate and causes of morbidity and mortality analysis. The mortality incidence rate of kids and adult goats were 0.638 and 0.302 per animal year respectively. The 25th, 50th and 75th percentile of survival time of kids were 5, 157 and 1,274 days respectively and of adult goats were 280, 828 and 1,557 days respectively. The present mortality rate is relatively larger than reports of boer cross breeding and evaluation research sites in Ethiopia as well as goat mortality prevalence abroad. Gastro-intestinal related diseases, pneumonia, weak kid, agalactia, mismothering and hear water (cowdriosis) were most important causes of mortality. Constant piecewise exponential regression analysis of risk factors indicates that breed, kid birth weight (BWT), doe post-partum weight (PPWT), birth type, birth year and precipitation variables were associated with (p-value < 0.05) kid mortality rate. Pure boer kids compared with CHG cross boer goat, are 2.505 times at higher probability of mortality (p ≤ 0.001). A 1 kilo gram increase of kid birth weight and dam PPWT reduces mortality probability by 32.5% (p-value ≤ 0.001) and 6.4% (p-value ≤ 0.001) respectively. Twin birth kids are1.512 times higher rate of mortality (p-value = 0.001) compared with single born kids. A one-millilitre increment of 15 days average precipitation significantly reduces kid mortality by 7.8% (p-value ≤ 0.001). Fleshing of does during early meeting to improve the post-partum weight of does and kids is also important to reduce both kid and doe mortality at and after kidding. Immunization of new introduced and kids to common endemic diseases in the area, extensive control of ticks to breakdown heart water transmission and use of proper comfortable housing to reduce stress of goats is recommended. Improving nutrition particularly during scarce grazing and browsing feed availability is important to improving the health and reducing mortality of goats in intensively managed goat farms.
Integrated silicon carbide modulator for CMOS photonics
Authors: Powell Keith , Li Liwei , Shams-Ansari Amirhassan , Wang Jianfu , Meng Debin , Sinclair Neil , Deng Jiangdong , Lončar Marko , Yi Xiaoke
Published: February 2021

The electro-optic modulator encodes electrical signals onto an optical carrier, and is essential for the operation of global communication systems and data centers that society demands. An ideal modulator results from scalable semiconductor fabrication and is integrable with electronics. Accordingly, it is compatible with complementary metal-oxide-semiconductor (CMOS) fabrication processes. Moreover, modulators using the Pockels effect enables low loss, ultrafast, and wide-bandwidth data transmission. Although strained silicon-based modulators could satisfy these criteria, fundamental limitations such as two-photon absorption, poor thermal stability and a narrow transparency window hinder their performance. On the other hand, as a wide bandgap semiconductor material, silicon carbide is CMOS compatible and does not suffer from these limitations. Due to its combination of color centers, high breakdown voltage, and strong thermal conductivity, silicon carbide is a promising material for CMOS electronics and photonics with applications ranging from sensors to quantum and nonlinear photonics. Importantly, silicon carbide exhibits the Pockels effect, but a modulator has not been realized since the discovery of this effect more than three decades ago. Here we design, fabricate, and demonstrate the first Pockels modulator in silicon carbide. Specifically, we realize a waveguide-integrated, small form-factor, gigahertz-bandwidth modulator that can operate using CMOS-level drive voltages on a thin film of silicon carbide on insulator. Furthermore, the device features no signal degradation and stable operation at high optical intensities (913 kW/mm2), allowing for high optical signal-to-noise ratios for long distance communications. Our work unites Pockels electro-optics with a CMOS platform to pave the way for foundry-compatible integrated photonics.
Intellectual Decline in a Patient with Migraine and APT1A2 Mutation: A Case Report
Authors: Wang Pian , Yang Yan-Rong , Zhang Hong-Bo , Wang Jiang-Hong , Wang Yan
Published: February 2021

Background: Hemiplegic migraine (HM) is a rare type of migraine with aura. Some reports have described the clinical manifestations in HM patients with the ATP1A2 mutation. But the impact of the ATP1A2 mutation on intelligence in HM patients has not been evaluated in detail. Here we report a patient with intellectual decline in specific area.Case presentation: A 15-year-old boy with an aura that included disturbances in consciousness, associated with fever, vomiting, hemiplegia, and aphasia. He was diagnosed HM with the ATP1A2 mutation before. He had trouble in mathematics and depicting three-dimensional things.Conclusions: The HM with ATP1A2 patient could develop permanent intellectual disabilities. Therefore, the intelligence quotient should be carefully and comprehensively evaluated.
Characterization and selection of Japanese electronic health record databases used as data sources for non-interventional observational studies
Authors: Wakabayashi Yumi , Eitoku Masamitsu , Suganuma Narufumi
Published: February 2021

Background

Interventional studies are the fundamental method for obtaining answers to clinical question. However, these studies are sometimes difficult to conduct because of insufficient financial or human resources or the rarity of the disease in question. One means of addressing these issues is to conduct a non-interventional observational study using electronic health record (EHR) databases as the data source, although how best to evaluate the suitability of an EHR database when planning a study remains to be clarified. The aim of the present study is to identify and characterize the data sources that have been used for conducting non-interventional observational studies in Japan and propose a flow diagram to help researchers determine the most appropriate EHR database for their study goals.
Methods

We compiled a list of published articles reporting observational studies conducted in Japan by searching PubMed for relevant articles published in the last 3 years and by searching database providers’ publication lists related to studies using their databases. For each article, we reviewed the abstract and/or full text to obtain information about data source, target disease or therapeutic area, number of patients, and study design (prospective or retrospective). We then characterized the identified EHR databases.
Results

In Japan, non-interventional observational studies have been mostly conducted using data stored locally at individual medical institutions (713/1463) or collected from several collaborating medical institutions (351/1463). Whereas the studies conducted with large-scale integrated databases (195/1463) were mostly retrospective (68.2%), 27.2% of the single-center studies, 46.2% of the multi-center studies, and 74.4% of the post-marketing surveillance studies, identified in the present study, were conducted prospectively.
Conclusions

Our analysis revealed that the non-interventional observational studies were conducted using data stored local at individual medical institutions or collected from collaborating medical institutions in Japan. Disease registries, disease databases, and large-scale databases would enable researchers to conduct studies with large sample sizes to provide robust data from which strong inferences could be drawn. Using our flow diagram, researchers planning non-interventional observational studies should consider the strengths and limitations of each available database and choose the most appropriate one for their study goals.
Trial registration
Not applicable.
Therapeutic vulnerability to PARP1,2 inhibition in RB1-mutant osteosarcoma
Authors: Zoumpoulidou Georgia , Mendoza Carlos Alvarez , Mancusi Caterina , Ahmed Ritika-Mahmuda , Denman Milly , Steele Christopher , Manji Jiten , Pillay Nischalan , Strauss Sandra , Mittnacht Sibylle
Published: February 2021

Loss-of-function mutations in the RB1 tumour suppressor are key drivers in cancer, including osteosarcoma. RB1 loss-of-function compromises genome-maintenance and hence could yield vulnerability to therapeutics targeting such processes. Here we demonstrate selective hypersensitivity to clinically-approved inhibitors of Poly-ADP-Polymerase1,2 inhibitors (PARPi) in RB1-mutated cancer cells including an extended panel of osteosarcoma-derived lines. PARPi treatment results in extensive cell death in RB1-mutated backgrounds and prolongs survival of mice carrying human RB1-mutated osteosarcoma grafts. PARPi sensitivity is not associated with canonical homologous recombination defect (HRd) signatures, which predict PARPi sensitivity in cancers with BRCA1,2 loss, but is accompanied by rapid activation of DNA replication checkpoint signalling, and active DNA replication is a prerequisite for sensitivity. Importantly, sensitivity in backgrounds with natural or engineered RB1 loss surpasses that seen in BRCA-mutated backgrounds where PARPi have established clinical benefit. Our work provides evidence that PARPi sensitivity extends beyond cancers identifiable by HRd and advocates PARP1,2 inhibition as a novel, personalised strategy for RB1-mutated osteosarcoma and other cancers.
The Effects of Soil Temperature From Soil Mulching and Harvesting Period On Phenol, Flavonoid And Antioxidant Contents of Java Tea (Orthosiphon Aristatus B.)
Authors: Komariah Komariah , Pitaloka Diora Diah Ayu , Batubara Irmanida , Nurcholis Waras , Sandrawati Apong , Setyawati Andriyana , Syamsiyah Jauhari , Dewi Widyatmani Sih
Published: February 2021

Purpose: The secondary metabolites of Java tea (Orthosiphon aristatus B) are effective to treat kidney inflammation, kidney stones, and other diseases. Abiotic factors have been known to determine the secondary metabolites contents of Java tea. This study aimed at evaluating the effects of soil temperature resulted from soil mulching and harvesting period on total phenol, flavonoid and antioxidant contents of Java tea. Methods: The research was carried out using nested with completely randomized design under a screen house at Karanganyar, Indonesia from July to December 2019. The first factor was soil mulching (control; black plastic mulch, transparent plastic mulch, biodegradable mulch and rice straw mulch) with three repetitions. The first factor was nested in second factor, namely harvesting period which consisted of two levels, i.e.: 80 and 100 days. The observation parameters were soil temperature of 10-minutes (maximum; mean; minimum and soil temperature based- growing degree days, GDD) with sensors and logger; plant growth (plant height, number of leaves, fresh and dry weight); and secondary metabolites including phenol, flavonoids and antioxidant. Results: The results confirmed the order of the highest to the lowest mean soil temperature was resulted under the transparent plastic mulch> straw > black plastic mulch >control > biodegradable plastic mulch (26.69 > 26.29 > 26.10 > 26.07 > 25.68 oC, respectively). The total phenol, flavonoids and antioxidant produced ranging from 193.75 – 412.50 mg GAE/ 100 g DW; 81.13 – 141.47 mg QE/ 100 g DW; and 1875.5 – 2144.4 µmol TE/g DW.Conclusion: Higher maximum soil temperature resulted into lower phenol content, while higher minimum soil temperature and shorter harvest period increased total flavonoid. Longer harvest period produced more total phenol and antioxidant due to bigger soil temperature based- Growing Degree Day (GDD).
Polyphenols Extracts From Didymosphenia Geminata (Lyngbye) Schmidt Altered the Motility and Viability of Daphnia Magna
Authors: Olivares-Ferretti Pamela , Chavez Viviana , Hernandez Klaudia , Peredo-Parada Matías , Parodi Jorge
Published: February 2021

The invasive diatom Didymosphenia geminata (Lyngbye) Schmidt, D. geminata has invaded the austral zone of Chile, causing significant ecological, scientific and societal concerns. We aimed to evaluate the viability and motility Daphnia magna (D. magna), as a biosensor for effects of D. geminata. Toxicity assays were performed in dilutions of river water alone (V/V dilution) and in river water contaminated with D. geminata (V/V dilution) or polyphenols extracted from D. geminata under controlled conditions and different time (acute 30 min and 7 hrs). Our results indicated that D. magna was sensitive to increasing concentrations of D. geminata extracts. We observed a 50% (IC50) viability reduction after 24 h of exposure to a 0.023 V/V dilution and the same value when using polyphenols from D. geminata; additionally, this treatment further reduced the motility capacity by 50% after 72 h. The D. magna organisms were acutely responsive, showing a 50% reduction in frequency at 15 min. We conclude that D. magna is sensitive to polyphenols produced by D. geminata in rivers, suggesting potential chronic toxic consequences on several aquatic species following exposure to these diatom substances.
Intraventricular T3 Reverses Chronic Restraint Stress-Induced Depressive-Like Behaviors: Inhibition of NF-κB/ NLRP3 Inflammasome Pathway in the Hippocampus
Authors: Mokhtari Tahmineh , El-Kenawy AymanEl-Meghawry , Hu Li
Published: February 2021

In this study, the effects of triiodothyronine (T3) were evaluated on the NLRP3 inflammasome complex formation in the hippocampus of the rat with restraint stress-induced depressive-like behaviors.Thirty-six Wistar male rats were randomly allocated to the following groups: Control, Model, and Model + T3. In Model or Model + T3 group, a single dose of PBS or T3 () was administered into the lateral ventricle. Depressive-like behaviors were induced by chronic restraint stress. The forced swimming (FST), tail suspension (TST), and open field (OFT) tests were used to investigate depression. The rats were sacrificed, and brain tissues were stored for molecular and pathological evaluations. Chronic stress increased the immobility of rats in the Model group according to FST, TST, and OFT (P < 0.05). T3 significantly improved depressive-like behaviors (P < 0.05). The gene expression and protein level of hippocampal NF-κB, NLRP3, ASC, and Caspase-1 significantly increased in the Model group compared to the control group (P < 0.05). The reduced hippocampal levels of NF-κB, NLRP3, ASC, and Caspase-1 were seen in the T3 group compared to the Model group (P < 0.05). Also, the Nissl staining of the CA1 region showed an increased number of dark neurons (P < 0.05) and reduced pyramidal layer thickness (P < 0.05) in the Model group. These histopathological alterations were changed by T3 administration compared to the Model group (P < 0.05). The findings of confirmed the therapeutic effects of intraventricularly T3 on depressive-like behaviors induced by restraint stress via surviving pyramidal neurons of the CA1 region and inhibition of NF-κB/NLRP3 inflammasome pathway.
The physics of pandemics with application to COVID19
Authors: Miller Stephen , Gunatilake Thanushika
Published: February 2021

Numerous models exist with the goal of modeling the propagation of COVID-19 and other epidemics or pandemics. These models include the SEIR (Susceptible-Exposed-Infected-Removed) model, Agent Based Models (ABM), and continuum models of reaction diffusion. Each of these modelling approaches contain multiple and sometimes intractable variables, resulting in large uncertainties in outcomes, thus restricting their utility in guiding local, national, and international governmental decisions for managing and controlling pandemics. There exists a need for a simple, fast, deterministic, scalable, and accurate model that captures the dominant physics of pandemic propagation. Here we propose such a model by adapting a physical earthquake/aftershock model to the COVID19 problem. The aftershock model revealed the physical basis for the Epidemic Type Aftershock Sequence (ETAS) model as a highly non-linear diffusion process, thus permitting a grafting of the underlying physical equations into a formulation for calculating infection pressure propagation in a pandemic-type model. Model results show excellent correlations with observed infection rates for all cases studied to date. In alphabetical order, these include Austria, Belgium, Brazil, France, Germany, Italy, Melbourne (AU), New Zealand, Spain, Sweden, Switzerland, UK, and the USA. Importantly, the model is predominantly controlled by one parameter α, which modulates societal compliance to governmental actions. We find that differing societal compliance between countries results in dramatically different outcomes given similar infection sources. These results provide an intuition-based approach to designing and implementing mitigation measures, with predictive capabilities for various mitigation scenarios.
Research on ride comfort of vibratory rollers: Part-1 Study on the effect of different cab isolation mounts
Authors: Kang Yan , Nguyen Vanliem , Guo Xiaoyan , Li Yuehan
Published: February 2021

In order to evaluate the ride quality of vibratory roller’s cab used the different isolation mounts including the traditional rubbers, hydraulics, and hydro-pneumatics, a nonlinear dynamics model of the vibratory roller under interaction of the deformable terrain and drum has been established based on Matlab/Simulink software. The root-mean-square (RMS) of the accelerations of the vertical driver’s seat and the cab’s pitch angle have been used as objective studies. The influence of damping and stiffness coefficients of different isolation mounts on the cab’s ride quality has been respectively simulated and analyzed under a hard ground at an excitation 28 Hz of the vibration drum. The research results indicate that the characteristics of non-linear damper and high-static stiffness of the hydro-pneumatic mounts can greatly reduce the vertical driver’s seat vibration and cab shaking when compared to vibratory roller’s cab using the traditional rubber mounts and hydraulic mounts under stiffness and damping coefficients of the vehicle and cab isolations. Particularly with the dynamics parameters of Kc= [0.8 to 1.2]×Kc0, Cc= [0.8 to 1.0]×Cc0, Kt,d= [0.6 to 1.0]×Kt0,d0, and Ct,d= [1.0 to 1.2]×Ct0,d0.
Multivariate analysis of sediment quality in River Ogbere, Ibadan, South-West Nigeria
Authors: Achi C. G. , Omoniyi A. M. , Coker A. O. , Sridhar M. K. C.
Published: February 2021

Heavy metals are pollutants of river sediments, and their concentration varies depending on parental material and anthropogenic inputs, thus it is important to distinguish between the natural and anthropogenic inputs. The objective of this study is to use different types of indexes to assess the current pollution status in Ogbere River sediment and select the best index to describe the sediment quality. The indexes used in this study were enrichment factor (EF), geoaccumulation index (Igeo) and principal component analysis (PCA). The PCA has an advantage over other index analyses as it reduces the dimensionality of the data set and thus used to support multivariate cluster analysis. From the study, a total of 12 sediment samples were collected in both seasons across six sampling location and pollution indexes indicated three things: firstly, the metal distribution profile in the sediment showed that the heavy metals analysed were lower than the maximum allowable limits stipulated by Department of Petroleum Resources (DPR); secondly, minor to extremely severe significant levels of enrichment and thirdly, practically uncontaminated to a moderately contaminated degree of contamination in Ogbere River during the study period. The PCA is considered more sensitive in the analysis of benthic changes as well as sediment quality. However, the heavy metal assessment indices are not only used for sediment quality. Biological testing and ecological analysis of existing community related to sediment contamination are further recommended in River Ogbere.
Capturing high-resolution water demand data in commercial buildings
Authors: Melville-Shreeve Peter , Cotterill Sarah , Butler David
Published: February 2021

Water demand measurements have historically been conducted manually, from meter readings less than once per month. Leading water service providers have begun to deploy smart meters to collect high-resolution data. A low-cost flush counter was developed and connected to a real-time monitoring platform for 119 ultra-low flush toilets in 7 buildings on a university campus to explore how building users influence water demand. Toilet use followed a typical weekly pattern in which weekday use was 92% ± 4 higher than weekend use. Toilet demand was higher during term time and showed a strong, positive relationship with the number of building occupants. Mixed-use buildings tended to have greater variation in toilet use between term time and holidays than office-use buildings. The findings suggest that the flush sensor methodology is a reliable method for further consideration. Supplementary data from the study's datasets will enable practitioners to use captured data for (i) forecast models to inform water resource plans; (ii) alarm systems to automate maintenance scheduling; (iii) dynamic cleaning schedules; (iv) monitoring of building usage rates; (v) design of smart rainwater harvesting to meet demand from real-time data; and (vi) exploring dynamic water pricing models, to incentivise optimal on-site water storage strategies.
Uncertainty analysis of monthly river flow modeling in consecutive hydrometric stations using integrated data-driven models
Authors: Amininia Karim , Saghebian Seyed Mahdi
Published: February 2021

The ﬂow assessment in a river is of vital interest in hydraulic engineering for ﬂood warning and evacuation measures. To operate water structures more efﬁciently, models that forecast river discharge are desired to be of high precision and certain degree of accuracy. Therefore, in this study, two artificial intelligence models, namely kernel extreme learning machine (KELM) and multivariate adaptive regression splines (MARS), were applied for the monthly river flow (MRF) modeling. For this aim, Mississippi river with three consecutive hydrometric stations was selected as case study. Using the previous MRF values during the period of 1950–2019, several models were developed and tested under two scenarios (i.e. modeling based on station's own data or previous station's data). Wavelet transform (WT) and ensemble empirical mode decomposition (EEMD) as data processing approaches were used for enhancing modeling capability. Obtained results indicated that the integrated models resulted in more accurate outcomes. Data processing enhanced the model's capability up to 25%. It was observed that the previous station's data could be applied successfully for MRF modeling when the station's own data were not available. The best-applied model dependability was assessed via uncertainty analysis, and an allowable degree of uncertainty was found in MRF modeling.
Impact of cyclone Amphan on the water, sanitation, hygiene, and health (WASH2) facilities of coastal Bangladesh
Authors: Rafa Nazifa , Jubayer Abu , Uddin Sayed Mohammad Nazim
Published: February 2021

The vulnerability of the underfunded water, sanitation, hygiene, and health (WASH2) facilities, particularly in the developing nations, is exacerbated by natural disasters. This study assessed the impacts of Amphan on the WASH2 facilities of the affected coastal areas of Bangladesh via a structured questionnaire survey, key informant interviews, and direct observation. The study reported that Amphan destroyed WASH2 facilities, where only 20% of the respondents were receiving WASH2 services afterwards. Many respondents had to rely on unsafe water sources after the cyclone hit. While the respondents used different kinds of water treatment methods, three-quarters of the respondents reported issues related to odor, taste, color, and/or others. The majority had to practice open defecation due to damage done to sanitation facilities. Amphan has also resulted in an onslaught of several WASH2 diseases in the study area, primarily skin disease and diarrhea. The study has exhibited how intense natural disasters can completely render WASH2 facilities useless, causing the communities affected to switch to unsafe practices to meet their needs. The affected communities are in urgent need of adequate and sustainable WASH2 facilities.
Indigenous knowledge systems based climate governance in water and land resource management in rural Zimbabwe
Authors: Mugambiwa S. S. , Makhubele J. C.
Published: February 2021

This paper interrogates indigenous knowledge systems (IKS) based climate governance in water and land resource management in under-resourced areas of Zimbabwe. Water and land resources are fundamental for smallholder farmers and their productivity. The concept of IKS plays a significant role in climate change adaptation in Zimbabwe's rural communities. Climate change has a considerable influence on the success of agricultural production in the rural communities of Zimbabwe. Hence, it becomes fundamental to assess the community-based methods of climate governance. Qualitative multiple case study exploratory designs were employed with data collected through individual interviews with smallholder farmers, and thematic content analysis was used to analyse data. This study found that enhancing and embracing IKS is of paramount importance for inclusion in local-level strategies in the development process with special reference to climate governance in water and land resource management, particularly in under-resourced communities. It also established that the use of IKS enhances communities' adaptive capacity and it should not be conducted at the expense of scientific methods but rather should be employed in order to complement the existing scientific global knowledge systems.
Water table dynamics beneath onsite wastewater systems in eastern North Carolina in response to Hurricane Florence
Authors: Humphrey Jr. Charles , Dillane Danielle , Iverson Guy , O'Driscoll Michael
Published: February 2021

Onsite wastewater treatment systems (OWTSs) are commonly used in eastern North Carolina. A vadose zone or vertical separation distance (VSD) between the OWTS drainfield trenches and groundwater is required for effective aerobic wastewater treatment. Extreme weather events, including hurricanes, can deliver significant rainfall that influences groundwater levels and reduces the VSD, thus also influencing the treatment of wastewater by the OWTS. Few studies have quantified the effects of storms on the VSD. Groundwater levels at three sites with the OWTS were monitored before, during, and after Hurricane Florence. Groundwater rose over 1.5 m within 9 h at the sites in response to rain from the hurricane but took more than 3.5 weeks to return to prestorm levels. Groundwater inundated the drainfield trenches for several days at two sites leading to direct discharge of wastewater to groundwater. The hydraulic gradient and the groundwater velocity increased during the storm and the groundwater flow direction shifted, leading to greater dispersion of wastewater impacted groundwater. The wastewater treatment efficiency of the soil-based OWTS in coastal areas may lessen over time because of rising water tables and reduced VSD. Individual pretreatment OWTSs, elevated drainfields, or centralized sewage treatment may be required in regions with shrinking VSDs.
Experimental investigations for assessing the influence of fly ash on the flow through porous media in Darcy regime
Authors: Chandel Abhishish , Shankar Vijay , Alam M. A.
Published: February 2021

Hydraulic conductivity plays a vital role in the studies encompassing explorations on flow and porous media. The study investigates the compaction characteristics of a river sand (Beas, Sutlej, and Ghaggar rivers) and fly ash mix in different proportions and evaluates four empirical equations for estimating hydraulic conductivity. Experiments show that an increase in the fly ash content results in a decrease in the maximum dry density (MDD) and an increase in the corresponding optimum moisture content (OMC) of sand–fly ash samples. MDD at optimum fly ash content was achieved at low water content, which resulted in less dry unit weight than that of typical conventional fill. In Beas, Sutlej, and Ghaggar sands the optimum fly ash content up to which the hydraulic conductivity value reduced uniformly was found to be 30, 45, and 40%, respectively. Any further increase in the fly ash content results in a negligible decrease in hydraulic conductivity value. The observed hydraulic conductivity of sand–fly ash mix lies in the range of silts, which emboldens the use of sand–fly ash mix as embankment material. Further, the evaluation of empirical equations considered in the study substantiates the efficacy of the Terzaghi equation in estimating the hydraulic conductivity of river sand-fly ash mix.