bluuebunny/crossref_metadata_2025 huggingface dataset:
Unraveling the Gordian knot: genetics and the troubled road to effective therapeutics for Alzheimer’s disease
Authors: Restifo Linda L
Published: October 2021

In the late 20th century, identification of the major protein components of amyloid plaques and neurofibrillary tangles provided a window into the molecular pathology of Alzheimer’s disease, ushering in an era of optimism that targeted therapeutics would soon follow. The amyloid-cascade hypothesis took hold very early, supported by discoveries that dominant mutations in APP, PSEN1, and PSEN2 cause the very rare, early-onset, familial forms of the disease. However, in the past decade, a stunning series of failed Phase-3 clinical trials, testing anti-amyloid antibodies or processing-enzyme inhibitors, prompts the question, What went wrong? The FDA’s recent controversial approval of aducanumab, despite widespread concerns about efficacy and safety, only amplifies the question. The assumption that common, late-onset Alzheimer’s is a milder form of familial disease was not adequately questioned. The differential timing of discoveries, including blood–brain–barrier-penetrant tracers for imaging of plaques and tangles, made it easy to focus on amyloid. Furthermore, the neuropathology community initially implemented Alzheimer’s diagnostic criteria based on plaques only. The discovery that MAPT mutations cause frontotemporal dementia with tauopathy made it even easier to overlook the tangles in Alzheimer’s. Many important findings were simply ignored. The accepted mouse models did not predict the human clinical trials data. Given this lack of pharmacological validity, input from geneticists in collaboration with neuroscientists is needed to establish criteria for valid models of Alzheimer’s disease. More generally, scientists using genetic model organisms as whole-animal bioassays can contribute to building the pathogenesis network map of Alzheimer’s disease.
Life-space Mobility in Older Men: The Role of Perceived Physical and Mental Fatigability
Authors: Moored Kyle D , Rosso Andrea L , Gmelin Theresa , Qiao Yujia (Susanna) , Carlson Michelle C , Cawthon Peggy M , Cauley Jane A , Glynn Nancy W
Published: October 2021

Background

Physical performance and fatigue can limit mobility within the larger environment (life-space mobility). It is unknown whether perceived fatigability, self-reported fatigue anchored to activity intensity and duration, is independently associated with life-space.

Methods

We assessed this cross-sectionally in Visit 4 (2014–2016) of the Osteoporotic Fractures in Men Study (MrOS; N = 1 672, Age: Mean = 84.2 ± 4.0 years). The Pittsburgh Fatigability Scale (PFS, range: 0–50; higher = greater fatigability) measured physical (Mean = 16.1 ± 9.4) and mental fatigability (Mean = 7.5 ± 7.9). Life Space Assessment scores incorporated level, frequency, and assistance used for life-space mobility (range: 0–120, higher = greater life-space mobility; life-space constriction: inability to leave neighborhood without assistance). Separate multiple linear and logistic regressions for physical and mental fatigability were sequentially adjusted for demographic, health/lifestyle, and performance measures.

Results

The mean life-space mobility score was 84.6 ± 21.8, and 18% (n = 296) of men had life-space constriction. Higher physical and mental fatigability were both associated with lower life-space mobility in models adjusted for health and lifestyle factors (Physical PFS: B = −2.37, 95% confidence interval [CI]: [−3.39, −1.35]; Mental PFS: B = −1.79, 95% CI: [−2.73, −0.84]). Men with higher fatigability also had increased risk of life-space constriction (Physical PFS: OR = 1.59, 95% CI: [1.32, 1.92]; Mental PFS: OR = 1.25, 95% CI: [1.08, 1.46]). Associations were larger in magnitude for physical versus mental fatigability. Adjusting for physical performance measures more strongly attenuated associations for physical compared to mental fatigability.

Conclusions

Fatigability is linked with real-world mobility in older men, independent of their physical health. This association may be driven by separate physical and cognitive mechanisms worth examining further in longitudinal studies.
Impact of Large Granular Lymphocyte Leukemia on Blood DNA Methylation and Epigenetic Clock Modeling in Fischer 344 Rats
Authors: Finesso Giovanni E , McDevitt Ross A , Roy Roshni , Brinster Lauren R , Di Francesco Andrea , Meade Theresa , de Cabo Rafael , Ferrucci Luigi , Perdue Kathy A
Published: October 2021

Age-dependent differences in methylation at specific cytosine–guanine (CpG) sites have been used in “epigenetic clock” formulas to predict age. Deviations of epigenetic age from chronological age are informative of health status and are associated with adverse health outcomes, including mortality. In most cases, epigenetic clocks are performed on methylation from DNA extracted from circulating blood cells. However, the effect of neoplastic cells in the circulation on estimation and interpretation of epigenetic clocks is not well understood. Here, we explored this using Fischer 344 (F344) rats, a strain that often develops large granular lymphocyte leukemia (LGLL). We found clear histological markers of LGLL pathology in the spleens and livers of 27 out of 61 rats aged 17–27 months. We assessed DNA methylation by reduced representation bisulfite sequencing with coverage of 3 million cytosine residues. Although LGLL broadly increased DNA methylation variability, it did not change epigenetic aging. Despite this, the inclusion of rats with LGLL in clock training sets significantly altered predictor selection probability at 83 of 121 commonly utilized CpG sites. Furthermore, models trained on rat samples that included individuals with LGLL had greater absolute age error than those trained exclusively rats free of LGLL (39% increase; p < .0001). We conclude that the epigenetic signals for aging and LGLL are distinct, such that LGLL assessment is not necessary for valid measures of epigenetic age in F344 rats. The precision and architecture of constructed epigenetic clock formulas, however, can be influenced by the presence of neoplastic hematopoietic cells in training set populations.
Paris Embraces Modern Art – But Not in Court: Opinion on the Cour d’Appel de Paris Decision – Jeff Koons v Franck Davidovici
Authors: Sutterer Moritz
Published: October 2021

In February 2021 the Paris Court of Appeal (Cour d’appel de Paris) rendered a decision against the US artist Jeff Koons, holding that he had infringed copyright relating to an advertisement photography that was more than 30 years old. Jeff Koons is famous for his Neo-pop Appropriation art – kitsch for some, a provocative breach with the traditional notion of art for others. It was not the first time Koons has had to defend his work in court. The French decision is particularly interesting, however, as it shows a very narrow understanding of the copyright exceptions. It is an illustrative example of the issues resulting from CJEU’s approach in Pelham, Spiegel Online and Funke Medien, where the Court held that once the recognisability of original elements has been established, the only way out of the infringement leads through the formal exceptions and limitations of the InfoSoc Directive. Based on the decision, I will reflect on the openness of copyright for art-specific forms of referencing and in particular analyse the subject matter and scope of the parody exception and contrast it with less formal approaches to consider new creative elements. I will also analyse the question of applicable law in internet cases.
COVID-19 and Outcomes in Patients With Inflammatory Bowel Disease: Systematic Review and Meta-Analysis
Authors: Tripathi Kartikeya , Godoy Brewer Gala , Thu Nguyen Minh , Singh Yuvaraj , Saleh Ismail Mohamed , Sauk Jenny S , Parian Alyssa M , Limketkai Berkeley N
Published: October 2021

Background

Our understanding of coronavirus disease 2019 (COVID-19) and its implications for patients with inflammatory bowel diseases (IBD) is rapidly evolving. We performed a systematic review and meta-analysis to investigate the epidemiology, clinical characteristics, and outcomes in IBD patients with COVID-19.

Methods

We searched PubMed, EMBASE, Cochrane Central, Clinicaltrials.gov, Web of Science, MedRxiv, and Google Scholar from inception through October 2020. We included studies with IBD patients and confirmed COVID-19. Data were collected on the prevalence, patient characteristics, pre-infection treatments for IBD, comorbidities, hospitalization, intensive care unit (ICU), admission, and death.

Results

Twenty-three studies with 51,643 IBD patients and 1449 with COVID-19 met our inclusion criteria. In 14 studies (n = 50,706) that included IBD patients with and without COVID-19, the prevalence of infection was 1.01% (95% confidence interval [CI], 0.92-1.10). Of IBD patients with COVID-19, 52.7% had Crohn’s disease, 42.2% had ulcerative colitis, and 5.1% had indeterminate colitis. Nine studies (n = 687) reported outcomes according to IBD therapy received. Compared with patients on corticosteroids, those on antitumor necrosis factor (anti-TNF) therapy had a lower risk of hospitalization (risk ratio [RR], 0.24; 95% CI, 0.16-0.35; P < .01; I2 = 0%) and ICU admission (RR, 0.10; 95% CI, 0.03-0.37; P < .01) but not death (RR, 0.16; 95% CI, 0.02-1.71; P = .13; I2 = 39%). Compared with patients on mesalamine, those on antitumor necrosis factor therapy had a lower risk of hospitalizations (RR, 0.37; 95% CI, 0.25-0.54), ICU admissions (RR, 0.20; 95% CI, 0.07-0.58), and death (0.21; 95% CI, 0.04-1.00). Comparing patients on immunomodulators vs mesalamine or anti-TNF therapy, there was no difference in these outcomes.

Conclusions

The prevalence of COVID-19 in IBD patients was low. Use of corticosteroids or mesalamine was significantly associated with worse outcomes, whereas use of anti-TNFs was associated with more favorable outcomes. Further investigation clarifying the mechanisms of these disparate observations could help identify risk and adverse outcome-mitigating strategies for patients with IBD.
Conserved Antigenic Structure of Contemporary Wild Poliovirus Type 1 Strains Endemic in Pakistan
Authors: Alam Muhammad Masroor , Ikram Aamir , Mahmood Nayab , Sharif Salmaan , Shaukat Shahzad , Fatmi Muhammad Qaiser , Angez Mehar , Khurshid Adnan , Rehman Lubna , Akhtar Ribqa , Mujtaba Ghulam , Arshad Yasir , Rana Muhammad Suleman , Yousaf Aneela , Zaidi Syed Sohail Zahoor , Salman Muhammad
Published: October 2021

Background

Elimination of poliovirus in Pakistan and Afghanistan is challenged by notions against the role of oral poliovirus vaccine (OPV) in eradicating contemporary wild poliovirus (WPV) strains.

Methods

A total of 1055 WPV type 1 (WPV1) strains isolated between 2013 and 2018 were categorized into 68 antigenic groups and tested for neutralization by OPV-derived antibodies. Molecular docking was conducted to determine neutralization efficiency of antibodies against WPV. The clinical significance of WPV1 variants was assessed to ascertain their role in patient outcomes.

Results

We found that 88% of WPV1 strains isolated from paralytic children belonged to a single antigenic lineage identical to the WPV1 strain detected in 1993. WPV1 antigenic variants were effectively neutralized by OPV-derived antibodies, with geometric mean titers comparable to the neutralization titers found for 3 strains in OPV (OPV1–3, 7.96–9.149 [95% confidence interval, 6.864–10.171]; WPV1 strains, 7.542–8.786 [6.493–9.869]). Docking examination underscored a strong antigen-antibody interaction despite variations within the viral protein 1 epitopes. There was no significant association (P = .78) with clinical prognosis among patients infected with antigenically diverse WPV1 strains and patient outcomes, including death.

Conclusions

Our findings substantiate the robustness of OPV for neutralizing the contemporary WPV1 strains endemic in Pakistan and Afghanistan. Vaccination coverage must be augmented to achieve early eradication.
Effectiveness of a Third Dose of BNT162b2 mRNA Vaccine
Authors: Saciuk Yaki , Kertes Jennifer , Shamir Stein Naama , Ekka Zohar Anat
Published: October 2021

A retrospective cohort study was carried out in a large Israeli health maintenance organization to determine vaccine effectiveness (VE) of a third dose of BNT162b2 vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Of nearly 1 million members receiving 2 doses of BNT162b2 in January–February 2021, infection rates (based on polymerase chain reaction results) were compared between those who received a third dose with those who did not during August–October 2021 (maximum, 70 days). Crude VE was 92.9% (95% confidence interval [CI], 92.6%–93.2%) and adjusted VE was 89.1% (95% CI, 87.5%–90.5%). We conclude that the third dose provides added protection against SARS-CoV-2 infection for those vaccinated 6 months ago.
Anxiety and the Onset of COVID-19: Examining Concerns of Historically Excluded Scholars
Authors: Ramos Jennifer M , Elliott Jamie Scalera , Fattore Christina , Breuning Marijke
Published: October 2021

The onset of the COVID-19 pandemic increased uncertainty, leading to questions about how it spread, how long it would last, and its long-term effects. In academia, many scholars worried about their positions and career advancement. Our research focuses on how different groups within academia coped during the initial period of the pandemic, with particular attention paid to the role of anxiety. We argue that vulnerable groups, such as historically excluded individuals, graduate students, and women, felt even higher levels of anxiety. We use original survey data collected from international relations and political science scholars during May 2020. We content analyze open-ended responses to illustrate the impacts of the pandemic on our participants’ work life, including research productivity, the job market, promotion, and tenure. These analyses reveal not only what different groups of scholars are concerned about, but also the different ways in which they discuss the pandemic. Our research aims to highlight the social and mental health effects of the pandemic, with an eye toward addressing inequalities in academia.
Effects of graded inclusion levels of raw garbanzo beans on apparent total tract digestibility, fecal quality, and fecal fermentative end-products and microbiota in extruded feline diets
Authors: Reilly Lauren M , He Fei , Rodriguez-Zas Sandra L , Southey Bruce R , Hoke Jolene M , Davenport Gary M , de Godoy Maria R C
Published: October 2021

Garbanzo beans (GB; Cicer arietinum) are a readily available pulse crop that have gained popularity as a plant-based protein source in the pet food industry. However, raw GB contain anti-nutritional factors that can reduce digestibility and cause digestive upsets in pets that are undesirable to owners. The objective of this study was to determine the effects of the inclusion of raw or cooked GB in extruded feline diets on macronutrient digestibility, gastrointestinal tolerance, and fermentative end-products in cats. Five diets were formulated to contain raw GB at 0%, 7.5%, 15%, or 30% or cooked GB at 30%. Ten adult, male cats (mean age: 1.0 ± 0.0 yr, mean BW: 4.7 ± 0.4 kg) were used in a replicated 5 × 5 Latin square design. Each period consisted of 14 d, with 10 d of diet adaptation followed by 4 d of total fecal and urine collection. At the end of each period, 4 mL of blood were collected and analyzed for a serum chemistry and complete blood count to ensure all animals remained healthy throughout the study. Cats were fed twice daily and food intake was calculated to maintain body weight. Food intake was highest (P < 0.05) for cats fed 0% raw GB (72.2 g/d, dry matter basis [DMB]) compared with GB inclusions of 7.5% or greater (average 70.3 g/d, DMB). Dry matter and organic matter apparent total tract digestibility (ATTD) were lowest (P < 0.05) for cats consuming the 30% cooked GB diet (77.3% and 81.7%, respectively). Cats fed 7.5% raw GB had greater (P < 0.05) crude protein ATTD (86.2%) than cats fed 15% raw GB (82.3%) or 30% cooked GB (81.6%). Total short-chain fatty acid concentrations were highest (P < 0.05) for 30% cooked GB at 682 μmol/g but not different (P > 0.05) than 15% GB (528 μmol/g) or 30% raw GB (591 μmol/g) diets. In terms of fecal microbial abundance, the predominant phyla were Firmicutes, Bacteroidota, and Actinobacteria. Cats fed the 0% GB diet had a greater relative abundance of Firmicutes (62.1%) and Fusobacteria (4.0%) than the remaining diets (average 54% and 1.6%, respectively). In conclusion, all inclusion levels of raw GB resulted in high digestibility (average > 80%) and ideal fecal scores (average 2.9), demonstrating their adequacy as a protein source in feline diets up to a 30% inclusion level.
Genetic inbreeding depression load for fertility traits in Pura Raza Española mares
Authors: Perdomo-González Davinia I , Molina Antonio , Sánchez-Guerrero María J , Bartolomé Ester , Varona Luis , Valera Mercedes
Published: October 2021

Fertility is a key factor in the economic success of horse farms. However, it has received little attention due to the difficulty of measuring fertility objectively. Since its studbook creation (1912), the Pura Raza Española (PRE) breed has been a closed population and become high in-bred resulting in inbreeding depression (poor phenotypic values). Nevertheless, heterogeneous effects of inbreeding depression have been detected among founders and nonfounders. The aims of this study were (1) to analyze the genetic parameters for reproductive traits in mares of the PRE horse breed and (2) to estimate, for the first time, the inbreeding depression load associated with common ancestors of the breed. A total of 22,799 mares were analyzed. Heritability estimates ranged from 0.05 (interval between first and second foaling) to 0.16 (age at first foaling), whereas inbreeding depression load ratios ranged from 0.06 (parturition efficiency at 6th foaling) to 0.17 (age at first foaling), for a partial inbreeding coefficient of 10%. Although heritability is related to the variability expressed in the population, inbreeding depression load ratios measure the potential variability, whether expressed in the population or not. Most correlations between additive and inbreeding depression load genetic values were significant (P < 0.001) and of low to moderate magnitude. Our results confirm that individual inbreeding depression loads allow us to select horses that have a genetic value resistant to the deleterious effects of inbreeding.
Massive Pediatric Burn Injury: A 10-Year Review
Authors: Martens Sally , Romanowksi Kathleen , Palmieri Tina , Greenhalgh David , Sen Soman
Published: October 2021

Advances in the care of burn-injured pediatric patients have improved mortality over the last 20 years. However, massive burn injuries (50% TBSA or greater) in pediatric patients, while overall rare, have a significant morbidity and mortality. The primary aim for this study is to analyze treatment and outcomes in massive pediatric burn injuries. A retrospective study of children with burn injuries 50% TBSA or greater who were admitted to Shriners Hospital for Children Northern California, from May 1, 2009 to May 22, 2020, was conducted. Data were collected from the electronic health records through a comprehensive chart review that included: patient demographics, past medical history, treatment interventions, and outcomes. This study included 69 patients (59.4% male) with a mean age of 8.7 ± 6 years. The median time from injury to admission was 2 (1–4) days. In this study, 63.8% of patients were from Mexico, 34.8% were from the United States, and 1% patient was from American Samoa. The median time from injury to admission was 2 (1−4) days. Mean TBSA was 66% ± 12%. The median TBSA of second-degree burns was 0 (0–6) %, and the mean TBSA of third-degree burns was 60% ± 16%. Forty percent of patients suffered an inhalation injury and 83% of patients received a tracheostomy. The median number of days requiring ventilator assistance was 26 (12–58) days. Mean length of hospitalization was 90 ± 60 days, with 61 ± 41 days spent in the intensive care unit. The mean number of surgical procedures was 6 ± 4. The time between surgical procedures was 12 ± 6 days. The median time from admission to the first surgical procedure was 1 (0–2) day. At the first procedure, a mean of 42% ± 15% TBSA of the burn injury was excised. Sixty-two percent of patients received autografting (22% ± 11% TBSA) and 52% of patients received allografting (27% ± 17% TBSA) during the first procedure. For survivors, the median number of inpatient occupational therapy encounters was 143.5 (83–215) and inpatient physical therapy encounters was 139.5 (81–215). Twenty-five percent of the patients included in this study died as a result of their burn injury. Multivariate regression revealed that sustaining an inhalation injury was a significant and independent predictor of death (odds ratio: 3.4, 95% confidence interval: 1.05 to 11, P = .04). Massive burn injuries in children required a very high number of surgical procedures and hospital resources. Most children who died as a result of their massive burn injury died within the first month of admission. Inhalation independently increases the risk of dying in pediatric patients with a massive burn injury.
Utilization of Acupuncture and Herbal Ointment Instead of Skin Graft Surgery for the Treatment of Burn Injuries: A Case Series and Literature Review
Authors: Kang Byungsoo , Sul Jae-Uk , Jeon Sangho , Cheon Seunghun , Leem Jungtae , Jo Seongjun
Published: October 2021

Skin graft surgery is a standard treatment that increases the survival rate of patients with burn injuries; however, it leaves many sequelae. Conventional external preparations for the treatment of burns also have various side effects. In this retrospective case study, we assessed the cases of four patients with topical third-degree burns who did not wish to undergo the skin graft surgeries recommended by medical doctors and were thus treated using traditional medicine alone. A Korean medicine doctor administered integrative traditional medicine treatment to the patients using acupuncture and herbal ointments. Analysis of the patients’ treatment photographs, quantitative evaluation indices, and vivid narratives suggested that their skin recovered well without adverse effects. Traditional Korean medicine treatment, including acupuncture and herbal ointment treatment, can be a new alternative therapeutic strategy for the treatment of patients with topical burns who do not want to undergo skin graft surgery or who have higher risks for poor surgical outcomes.
Examination of Health Information Needs of Caregivers of and Individuals with Burn Injuries
Authors: Jones Tammie M , Bhanji Alaanah , Ahuja Geeta , Bakhtari Ramez , Cai Xinsheng “Cindy” , Garfinkel Steven , Gerber Lynn , Weinstein Ali A
Published: October 2021

Burns are a leading cause of trauma worldwide with about 450,000 burn injuries being treated at medical facilities in the United States each year. Finding relevant information on the long-term consequences of burn injuries is a significant challenge for many individuals with burn injuries and their caregivers. This qualitative study aimed to identify how individuals with burn injuries and caregivers of individuals with burn injuries prefer to access and use health information, identify obstacles to accessing useful information, and identify information most needed by burn survivors and caregivers. Participants were recruited through hospital listservs, websites, social media, and word of mouth from across the United States. Semi-structured interviews were conducted with 23 individuals, 12 with burn injuries and 11 caregivers of individuals with burn injuries. Three specific needs were identified: (1) more direction from health professionals in finding health information relevant to burn injuries; (2) more internet-based access points that connect individuals to appropriate support networks; and (3) more support for long-term consequences of burn injuries, specifically with psychological, social, and other chronic physical issues. Participants identified various needs in finding relevant health information, thereby highlighting gaps in current literature and the dissemination of current literature. One potential way to address these deficiencies is to consider user-centered design principles in developing research, by more directly involving individuals with burn injuries and caregivers as part of the research team.
Screening Digital Breast Tomosynthesis: Radiation Dose Among Patients With Breast Implants
Authors: Vu Nhu Q , Bice Curran , Garrett John , Longhurst Colin , Belden Daryn , Haerr Carolyn , Prue Lucinda , Woods Ryan W
Published: October 2021

Objective

To compare the mean glandular dose (MGD), cancer detection rate (CDR), and recall rate (RR) among screening examinations of patients with breast implants utilizing various digital breast tomosynthesis (DBT)-based imaging protocols.

Methods

This IRB-approved retrospective study included 1998 women with breast implants who presented for screening mammography between December 10, 2013, and May 29, 2020. Images were obtained using various protocol combinations of DBT and 2D digital mammography. Data collected included MGD, implant type and position, breast density, BI-RADS final assessment category, CDR, and RR. Statistical analysis utilized type II analysis of variance and the chi-square test.

Results

The highest MGD was observed in the DBT only protocol, while the 2D only protocol had the lowest (10.29 mGy vs 5.88 mGy, respectively). Statistically significant difference in MGD was observed across protocols (P < 0.0001). The highest per-view MGD was among DBT full-field (FF) views in both craniocaudal and mediolateral oblique projections (P < 0.0001). No significant difference was observed in RR among protocols (P = 0.17). The combined 2D (FF only) + DBT implant-displaced (ID) views protocol detected the highest number of cancers (CDR, 7.2 per 1000), but this was not significantly different across protocols (P = 0.48).

Conclusion

The combination of 2D FF views and DBT ID views should be considered for women with breast implants in a DBT-based screening practice when aiming to minimize radiation exposure without compromising the sensitivity of cancer detection. Avoidance of DBT FF in this patient population is recommended to minimize radiation dose.
Chronobiological Effect on the Reproductive Behavior of Chrysomya megacephala (Diptera: Calliphoridae)
Authors: Chen Feng-Hsuan , Shiao Shiuh-Feng
Published: October 2021

The most widely used entomological method of determining the time since death (minimum postmortem interval, mPMI) has been calculating the developmental time of blow flies (Diptera: Calliphoridae) on the deceased body. However, because blow flies are known to be diurnal, nocturnal oviposition has been excluded from standard mPMI calculations. This has been challenged by recent studies demonstrating nocturnal oviposition due to an unknown reason. Therefore, this study investigated the role of chronobiology. We recorded the locomotion amount and pattern of Chrysomya megacephala (Fabricius, 1794) (Diptera: Calliphoridae) under different chronobiological conditions and examined whether Ch. megacephala can oviposit under nighttime conditions in field and laboratory settings. Subjects were found to have a daily activity pattern under normal darkness conditions (12:12 L:D) and under continuous darkness (DD), but they exhibited no pattern under continuous light (LL). Free-running period was approximately 1,341 min/d (22.35 h/d). In the field, no flies were observed during nighttime. Oviposition occurred in the laboratory setting during daytime with no lights and during nighttime with artificial lights. Free-running subjects oviposited in both active and resting periods, with more eggs laid during active than resting periods. The result of this study indicates it is possible to induce oviposition behavior during evening hours on Ch. megacephala. However, this was only observed in the laboratory setting and could only happen during the flies’ subjective day.
Expansive and Diverse Phenotypic Landscape of FieldAedes aegypti(Diptera: Culicidae) Larvae with Differential Susceptibility to Temephos: Beyond Metabolic Detoxification
Authors: Morgan Jasmine , Salcedo-Sora J Enrique , Triana-Chavez Omar , Strode Clare
Published: October 2021

Arboviruses including dengue, Zika, and chikungunya are amongst the most significant public health concerns worldwide. Arbovirus control relies on the use of insecticides to control the vector mosquito Aedes aegypti (Linnaeus), the success of which is threatened by widespread insecticide resistance. The work presented here profiled the gene expression of Ae. aegypti larvae from field populations of Ae. aegypti with differential susceptibility to temephos originating from two Colombian urban locations, Bello and Cúcuta, previously reported to have distinctive disease incidence, socioeconomics, and climate. We demonstrated that an exclusive field-to-lab (Ae. aegypti strain New Orleans) comparison generates an over estimation of differential gene expression (DGE) and that the inclusion of a geographically relevant field control yields a more discrete, and likely, more specific set of genes. The composition of the obtained DGE profiles is varied, with commonly reported resistance associated genes including detoxifying enzymes having only a small representation. We identify cuticle biosynthesis, ion exchange homeostasis, an extensive number of long noncoding RNAs, and chromatin modelling among the differentially expressed genes in field resistant Ae. aegypti larvae. It was also shown that temephos resistant larvae undertake further gene expression responses when temporarily exposed to temephos. The results from the sampling triangulation approach here contribute a discrete DGE profiling with reduced noise that permitted the observation of a greater gene diversity, increasing the number of potential targets for the control of insecticide resistant mosquitoes and widening our knowledge base on the complex phenotypic network of the Ae. aegypti response to insecticides.
Selective Host Attachment byIxodes scapularis(Acari: Ixodidae): Tick–Lizard Associations in the Southeastern United States
Authors: Ginsberg Howard S , Hickling Graham J , Pang Genevieve , Tsao Jean I , Fitzgerald Meghan , Ross Breann , Rulison Eric L , Burke Russell L
Published: October 2021

Questing behavior and host associations of immature blacklegged ticks, Ixodes scapularis Say, from the southeastern United States are known to differ from those in the north. To elucidate these relationships we describe host associations of larval and nymphal I. scapularis from 8 lizard species sampled from 5 sites in the southeastern U.S. Larvae and nymphs attached in greater numbers to larger lizards than to smaller lizards, with differential levels of attachment to different lizard species. Blacklegged ticks are generally attached to skinks of the genus Plestiodon in greater numbers per unit lizard weight than to anoles (Anolis) or fence lizards (Sceloporus). The broad-headed skink, Plestiodon laticeps (Schneider), was a particularly important host for immature I. scapularis in our study and in several previous studies of tick–host associations in the southeast. Blacklegged ticks show selective attachment to Plestiodon lizard hosts in the southeast, but whether this results from behavioral host preferences or from ecological factors such as timing or microhabitat distributions of tick questing and host activity remains to be determined.
Linking Organizational Capacity and Performance: The Case of Probation and Medicaid Reform in California Counties
Authors: Koerner Aeric A H , Johnston Jocelyn M
Published: October 2021

This article examines whether and how the capacity of a street-level organization moderates its ability to perform effectively in the context of a public program reform. We use the case of California probation departments during the phased implementation of the state’s Low-Income Health Program, a major Medicaid reform that offered critical new services for many probation citizens/clients, namely, mental health and substance abuse treatment. We exploit six years of monthly California county-level probation department data to conduct quasi-experimental difference-in-differences analyses. Results indicate that in those counties that had activated the reform, probation departments with greater capacity achieved higher rates of probation completion success when compared to departments with lower capacity. The analysis implies that organizations improved most when departments benefitted from a combination of reform-generated resources and more robust organizational capacity.
Fistulating diverticular disease masquerading as a peri-anal abscess: a laparoscopic approach to management
Authors: Schmidt Emily , Corbitt Matthew , Kulendran Krish , Ruggiero Boris
Published: October 2021

We present a rare case of complicated sigmoid diverticulitis presenting as a peri-anal abscess from an extra-sphincteric fistulous tract. This presentation of a colocutaneous peri-anal abscess is extremely rare, with only a handful of cases described in the literature. Most are managed with an open sigmoid colectomy, however, this case was successfully managed laparoscopically. It highlights the need to consider extra-levator causes of peri-anal abscess, such as pelvic sepsis causing fistulating disease, and to consider early magnetic resonance imaging if there is clinical suspicion of underlying pathology. It also demonstrates that a safe and potentially less morbid outcome is possible via laparoscopic approach when compared to traditional open surgical approach.
Metagenomics-driven rapid diagnosis of an imported fatal case of rare amoebic meningoencephalitis
Authors: Guan Qingtian , Alhuthali Bushra , Mfarrej Sara , Halim Magid Abdel , Almaghrabi Reem S , Pain Arnab
Published: October 2021

We identified Naegleria fowleri as the aetiologic agent from cerebrospinal fluid of a patient with a travel history to Karachi. We demonstrate the benefit of metagenomics-based rapid diagnosis of primary amoebic meningoencephalitis when routine clinical tests fail to provide a definitive diagnosis. We reconstructed the N. fowleri genome.
Casualties of the Spanish Army in Cuba During the “Long War” of 1868-1878
Authors: Nieves J Edwin , Pace April Adams
Published: October 2021

Spanish continental soldiers were ill prepared for the environmental conditions they encountered in the first of three wars for Cuban independence. The disease fatality rate was over 80% with yellow fever the most prevalent disease. Another 7% of these soldiers died in battle or from their combat wounds.
Ideafix: a decision tree-based method for the refinement of variants in FFPE DNA sequencing data
Authors: Tellaetxe-Abete Maitena , Calvo Borja , Lawrie Charles
Published: October 2021

Increasingly, treatment decisions for cancer patients are being made from next-generation sequencing results generated from formalin-fixed and paraffin-embedded (FFPE) biopsies. However, this material is prone to sequence artefacts that cannot be easily identified. In order to address this issue, we designed a machine learning-based algorithm to identify these artefacts using data from >1 600 000 variants from 27 paired FFPE and fresh-frozen breast cancer samples. Using these data, we assembled a series of variant features and evaluated the classification performance of five machine learning algorithms. Using leave-one-sample-out cross-validation, we found that XGBoost (extreme gradient boosting) and random forest obtained AUC (area under the receiver operating characteristic curve) values >0.86. Performance was further tested using two independent datasets that resulted in AUC values of 0.96, whereas a comparison with previously published tools resulted in a maximum AUC value of 0.92. The most discriminating features were read pair orientation bias, genomic context and variant allele frequency. In summary, our results show a promising future for the use of these samples in molecular testing. We built the algorithm into an R package called Ideafix (DEAmination FIXing) that is freely available at https://github.com/mmaitenat/ideafix.
Quantifying the tissue-specific regulatory information within enhancer DNA sequences
Authors: Benner Philipp , Vingron Martin
Published: October 2021

Recent efforts to measure epigenetic marks across a wide variety of different cell types and tissues provide insights into the cell type-specific regulatory landscape. We use these data to study whether there exists a correlate of epigenetic signals in the DNA sequence of enhancers and explore with computational methods to what degree such sequence patterns can be used to predict cell type-specific regulatory activity. By constructing classifiers that predict in which tissues enhancers are active, we are able to identify sequence features that might be recognized by the cell in order to regulate gene expression. While classification performances vary greatly between tissues, we show examples where our classifiers correctly predict tissue-specific regulation from sequence alone. We also show that many of the informative patterns indeed harbor transcription factor footprints.
ParsVNN: parsimony visible neural networks for uncovering cancer-specific and drug-sensitive genes and pathways
Authors: Huang Xiaoqing , Huang Kun , Johnson Travis , Radovich Milan , Zhang Jie , Ma Jianzhu , Wang Yijie
Published: October 2021

Prediction of cancer-specific drug responses as well as identification of the corresponding drug-sensitive genes and pathways remains a major biological and clinical challenge. Deep learning models hold immense promise for better drug response predictions, but most of them cannot provide biological and clinical interpretability. Visible neural network (VNN) models have emerged to solve the problem by giving neurons biological meanings and directly casting biological networks into the models. However, the biological networks used in VNNs are often redundant and contain components that are irrelevant to the downstream predictions. Therefore, the VNNs using these redundant biological networks are overparameterized, which significantly limits VNNs’ predictive and explanatory power. To overcome the problem, we treat the edges and nodes in biological networks used in VNNs as features and develop a sparse learning framework ParsVNN to learn parsimony VNNs with only edges and nodes that contribute the most to the prediction task. We applied ParsVNN to build cancer-specific VNN models to predict drug response for five different cancer types. We demonstrated that the parsimony VNNs built by ParsVNN are superior to other state-of-the-art methods in terms of prediction performance and identification of cancer driver genes. Furthermore, we found that the pathways selected by ParsVNN have great potential to predict clinical outcomes as well as recommend synergistic drug combinations.
The Impact of COVID-19 on Outpatient Antibiotic Prescriptions in Ontario, Canada; An Interrupted Time Series Analysis
Authors: Kitano Taito , Brown Kevin A , Daneman Nick , MacFadden Derek R , Langford Bradley J , Leung Valerie , So Miranda , Leung Elizabeth , Burrows Lori , Manuel Douglas , Bowdish Dawn M E , Maxwell Colleen J , Bronskill Susan E , Brooks James I , Schwartz Kevin L
Published: October 2021

Background

The coronavirus disease 2019 (COVID-19) pandemic has potentially impacted outpatient antibiotic prescribing. Investigating this impact may identify stewardship opportunities in the ongoing COVID-19 period and beyond.

Methods

We conducted an interrupted time series analysis on outpatient antibiotic prescriptions and antibiotic prescriptions/patient visits in Ontario, Canada, between January 2017 and December 2020 to evaluate the impact of the COVID-19 pandemic on population-level antibiotic prescribing by prescriber specialty, patient demographics, and conditions.

Results

In the evaluated COVID-19 period (March–December 2020), there was a 31.2% (95% CI, 27.0% to 35.1%) relative reduction in total antibiotic prescriptions. Total outpatient antibiotic prescriptions decreased during the COVID-19 period by 37.1% (95% CI, 32.5% to 41.3%) among family physicians, 30.7% (95% CI, 25.8% to 35.2%) among subspecialist physicians, 12.1% (95% CI, 4.4% to 19.2%) among dentists, and 25.7% (95% CI, 21.4% to 29.8%) among other prescribers. Antibiotics indicated for respiratory infections decreased by 43.7% (95% CI, 38.4% to 48.6%). Total patient visits and visits for respiratory infections decreased by 10.7% (95% CI, 5.4% to 15.6%) and 49.9% (95% CI, 43.1% to 55.9%). Total antibiotic prescriptions/1000 visits decreased by 27.5% (95% CI, 21.5% to 33.0%), while antibiotics indicated for respiratory infections/1000 visits with respiratory infections only decreased by 6.8% (95% CI, 2.7% to 10.8%).

Conclusions

The reduction in outpatient antibiotic prescribing during the COVID-19 pandemic was driven by less antibiotic prescribing for respiratory indications and largely explained by decreased visits for respiratory infections.
Severe dyslipidemia associated with diabetic ketoacidosis in newly diagnosed female of type 1 diabetes mellitus
Authors: Chreitah Ahmad , Hijazia Kheria , Doya Leen , Salloum Alaa
Published: October 2021

Diabetic ketoacidosis (DKA) is considered as a serious complication of type 1 diabetes mellitus in pediatrics. Severe dyslipidemia in DKA is a rare eventuality.

We report on a 10-year-old female presented with severe DKA. The serum was lipemic with severe hypertriglyceridemia and hypercholesterolemia. Laboratory workup: the values of glycemia, sodium and HbA1c were misleading; a method of dilution was used to obtain the correct values. Triglyceride and cholesterol returned gradually to normal levels only with the management of DKA without any complication.

Mild dyslipidemia is a common feature in DKA, but severe dyslipidemia is a very rare event whose pathophysiology is not completely elucidated. It needs close surveillance because it might be responsible for acute pancreatitis and lipidemia retinalis.
Herpes simplex esophagitis in an immunocompetent host: a case report
Authors: Upadhaya Regmi Binit , Subedi Ram Chandra , Mandal Sujit Kumar , Kunwar Shova , Karki Binod
Published: October 2021

Esophagitis caused by Herpes Simplex virus is a well-recognized opportunistic infection in the immunocompromised or severely ill host. However, it is uncommon in otherwise immunocompetent host. It usually responds well to a course of acyclovir. We report a case of young female without any other immunocompromised state who presented with severe dysphagia. She was diagnosed endoscopically and later with histopathology and recovered well after a course of acyclovir.
Meningitis retention syndrome associated with complicated mild encephalitis/encephalopathy with reversible splenial lesion in a young adult patient: a case report
Authors: Hidaka Masaoki , Sawamura Natsuki , Yokoi Mio , Mezuki Satomi , Osaki Masato , Arakawa Shuji , Akiyama Tomoaki , Yamaguchi Shinya , Sayama Tetsuro , Kitazono Takanari
Published: October 2021

Meningitis retention syndrome (MRS), comprising aseptic meningitis and urinary retention, is a self-limiting disease that resolves within a few weeks. Refractory urinary retention and encephalitic syndromes are rare. A 32-year-old man presented with acute fever and headache followed by acute urinary retention (UT). Neurological examination revealed meningeal irritation, UT, constipation and ataxic gait. The cerebrospinal fluid showed mononuclear leukocytosis, and the etiological examination was negative. We suspected MRS. However, magnetic resonance imaging demonstrated an abnormally intense lesion in the splenium of the corpus callosum (SCC). He also developed delirium on day 4 of hospitalization. We diagnosed the patient with MRS associated with mild encephalitis/encephalopathy with a reversible splenial lesion (MERS). While his delirium and constipation improved, and the SCC lesion disappeared, UT was refractory and required 6 months to complete recovery. Our case suggests that severe MRS can exhibit refractory UT and may associate with MERS.
Sarcoidosis with secondary recurrent right-sided chylothorax and chylous ascites in a Caucasian male patient
Authors: Jagannathan Sujaay Hari , Winn Caleb M , Nayar Arun P , Koussa Ghassan J , Brenner Carol A
Published: October 2021

Sarcoidosis is a rare multisystem autoimmune disease characterized by the presence of non-caseating granulomas in involved organs. We report a novel case of a 61-year-old Caucasian male with sarcoidosis presenting with recurrent chylothorax and chylous ascites. Pleural and ascitic fluid analysis revealed high triglyceride levels, consistent with chylothorax and chylous ascites, respectively. Common etiologies of chylous fluid such as thoracic duct surgical trauma, malignancy and infection were all excluded. Sarcoidosis was confirmed by the presence of non-caseating granulomas on a mediastinal lymph node biopsy. Conservative treatment with low-fat diet, prednisone, octreotide and multiple thoracenteses failed to effectively resolve the chylothorax. Surgical interventions with pleurodesis and thoracic duct ligation were performed, leading to the complete resolution of the chylous effusion and ascites.
Engineering of layered metal dichalcogenides: introducing imperfections to make it perfect
Authors: Basu Parbati , Chatterjee Kuntal
Published: October 2021

In the past decade, the surge in research of layered metal dichalcogenides (LMDs) has already demonstrated the tremendous potentiality of this particular category of materials towards technology. But in parallel, it is also established that to make them technology-perfect meticulous engineering to impose ‘imperfections’ within the materials is inevitable. So exploring different LMD with inexorable and appropriate engineering techniques for the enhancement of their functionality is the burning issue for materials scientists. This review comprehensively focuses on different pathways of introducing ‘imperfections’ within various LMDs, mainly by engineering the thickness, morphology, defect, doping and phase. Based on recent progress thickness and shape engineering of LMDs have been discussed with their success and modulation by defect has been examined in detail. Doping and phase engineering of LMDs have also been illustrated with the light of development till now. Finally, challenges and opportunities associated with this research direction are highlighted.