cssi/SciSciGPT-SciSciNet huggingface dataset:
Countable State Markov Shifts

This chapter is concerned with countable state Markov shifts. The first problem is to extend the Perron-Frobenius theory to nonnegative, countably infinite matrices. There are several difficulties. Countable matrices are classified by recurrence properties. There are three classes: positive recurrent, null recurrent and transient. The corresponding version of the Perron-Frobenius Theorem is successively weakened for each class. The necessary matrix theory is treated in the first section. The treatment is complete and there are a number of examples.
The Influence of Component Alignment and Ligament Properties on Tibiofemoral Contact Forces in Total Knee Replacement

The study objective was to investigate the influence of coronal plane alignment and ligament properties on total knee replacement (TKR) contact loads during walking. We created a subject-specific knee model of an 83-year-old male who had an instrumented TKR. The knee model was incorporated into a lower extremity musculoskeletal model and included deformable contact, ligamentous structures, and six degrees-of-freedom (DOF) tibiofemoral and patellofemoral joints. A novel numerical optimization technique was used to simultaneously predict muscle forces, secondary knee kinematics, ligament forces, and joint contact pressures from standard gait analysis data collected on the subject. The nominal knee model predictions of medial, lateral, and total contact forces during gait agreed well with TKR measures, with root-mean-square (rms) errors of 0.23, 0.22, and 0.33 body weight (BW), respectively. Coronal plane component alignment did not affect total knee contact loads, but did alter the medial-lateral load distribution, with 4 deg varus and 4 deg valgus rotations in component alignment inducing +17% and -23% changes in the first peak medial tibiofemoral contact forces, respectively. A Monte Carlo analysis showed that uncertainties in ligament stiffness and reference strains induce ±0.2 BW uncertainty in tibiofemoral force estimates over the gait cycle. Ligament properties had substantial influence on the TKR load distributions, with the medial collateral ligament and iliotibial band (ITB) properties having the largest effects on medial and lateral compartment loading, respectively. The computational framework provides a viable approach for virtually designing TKR components, considering parametric uncertainty and predicting the effects of joint alignment and soft tissue balancing procedures on TKR function during movement.
Who is Publishing in Facial Cosmetic Surgery? A Citation Analysis Across Specialties Over Five Decades.

Background Competition among our sister cosmetic specialties continues to increase. Once a field dominated by plastic surgeons, there is a clear trend toward increased competition from core and non-core disciplines. While these marketplace trends are obvious, how such competition has affected academia or peer reviewed publications is less clear. Objectives We analyzed the most cited peer reviewed facial aesthetic literature over the past five decades to see if marketplace trends are echoed in a similar manner across the academic disciplines of plastic surgery, otolaryngology, dermatology, and ophthalmology. Methods The top 50 cited articles for each decade from the 1970s to the 2010s were identified for the topics of facelift, rhinoplasty, browlift, and blepharoplasty using the Thomson/Reuters Web of Knowledge. Data collected were: the number of citations/article, first authors' specialty affiliation, and journal specialty affiliation. Data were plotted graphically and trends were analyzed. Results With regards to first authorship, plastic surgery had the highest percentage across all surgeries at every time point, except for rhinoplasty from 2010-present, when otolaryngology had a higher percentage (48% vs 40%). Observed trends demonstrated: (1) increasing contributions from otolaryngology in rhinoplasty, facelift, and browlift; and (2) increasing contributions from ophthalmology in blepharoplasty. Plastic surgery journals are the most common platform for publication across all four surgeries. Conclusions Plastic surgeons, and plastic surgery journals, still remain a strong force in academic facial cosmetic surgery. However, it appears that the competition from non-plastic surgeons observed in clinical practice is being mirrored in the area of journal publications. We as a specialty need to continue to strive for high quality academic productivity. [10.1093/asj/sjv240][1] [1]: /lookup/doi/10.1093/asj/sjv240
Integrated thermal-structural finite element analysis

An integrated thermal-structural finite element approach for efficient coupling of thermal and structural analysis is presented. An integrated thermal-structural rod element is developed and used in four thermal-structural applications; the accuracy of this integrated approach is illustrated by comparisons with the customary approach of finite difference thermal-finite element structural analyses. Results show that integrated thermal-structural analysis of structures modeled with rod elements is more accurate than conventional analysis, and that its further development promises significant results.
Clear Cell Papillary Renal Cell Carcinoma: A Novel Category of Renal CellNeoplasm

Copyright: © 2012 Alexiev BA. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Clear cell Renal Cell Carcinoma (clear cell RCC) and papillary Renal Cell Carcinoma (papillary RCC) are the most common carcinomas of the renal tubular epithelium and distinguishing them from one another is important because they have different prognoses [1-3]. Although most of the time they can be distinguished easily in routine sections, occasionally, overlapping morphologic findings make classification difficult. Rarely, RCC are encountered in which there are areas of papillary architecture, but there are extensive populations of cells with clear cytoplasm [1-3]. In this situation, it is unclear whether they should be classified as clear cell RCC or papillary RCC. Recently, a distinctive tumor characterized by papillary architecture and composed entirely of clear cells has been described as arising in kidneys with or without end-stage renal disease and is designated as ‘‘Clear Cell Papillary Renal Cell Carcinoma’’ (CCPC) [1-3].
Indocyanine green SPY elite-assisted sentinel lymph node biopsy in cutaneous melanoma.

Background Sentinel lymph node biopsy is the standard of care for intermediate-depth and high-risk thin melanomas. Recently, indocyanine green and near-infrared imaging have been used to aid in sentinel node biopsy. The present study aimed to determine the feasibility of sentinel lymph node biopsy with indocyanine green SPY Elite navigation and to critically evaluate the technique compared with the standard modalities. Methods A retrospective review of 90 consecutive cutaneous melanoma patients who underwent sentinel lymph node biopsy was performed. Two cohorts were formed: group A, which had sentinel lymph node biopsy performed with blue dye and radioisotope; and group B, which had sentinel lymph node biopsy performed with radioisotope and indocyanine green SPY Elite navigation. The cohorts were compared to assess for differences in localization rates, sensitivity and specificity of sentinel node identification, and length of surgery. Results The sentinel lymph node localization rate was 79.4 percent using the blue dye method, 98.0 percent using the indocyanine green fluorescence method, and 97.8 percent using the radioisotope/handheld gamma probe method. Indocyanine green fluorescence detected more sentinel lymph nodes than the vital dye method alone (p = 0.020). A trend toward a reduction in length of surgery was noted in the SPY Elite cohort. Conclusions Sentinel lymph node mapping and localization in cutaneous melanoma with the indocyanine green SPY Elite navigation system is technically feasible and may offer several advantages over current modalities, including higher sensitivity and specificity, decreased number of lymph nodes sampled, decreased operative time, and potentially lower false-negative rates. Clinical question/level of evidence Diagnostic, II.
Towards Better Understanding of Academic Search

Academics have relied heavily on search engines to identify and locate research manuscripts that are related to their research areas. Many of the early information retrieval sys- tems and technologies were developed while catering for li- brarians to help them sift through books and proceedings, followed by recent online academic search engines such as Google Scholar and Microsoft Academic Search. In spite of their popularity among academics and importance to academia, the usage, query behaviors, and retrieval models for aca- demic search engines have not been well studied. To this end, we study the distribution of queries that are received by an academic search engine. Furthermore, we delve deeper into academic search queries and classify them into navigational and informational queries. This work in- troduces a definition for navigational queries in academic search engines under which a query is considered naviga- tional if the user is searching for a specific paper or docu- ment. We describe multiple facets of navigational academic queries, and introduce a machine learning approach with a set of features to identify such queries.
Inzidenz von Malignomen nach Nierentransplantation

Vom 1.1.1971 bis 30.6.1995 wurden an der Chirurgischen Universitatsklinik Freiburg 1584 Nierentransplantationen bei 1352 Patienten durchgefuhrt. Das Durchschnittsalter betrug 41 Jahre (1–71 Jahre). Die immunsuppressive Therapie wurde bis Juni 1983 mit Prednisolon und Azathioprin durchgefuhrt. Ab Juli 1983 erfolgte die Umstellung auf eine Triple-Therapie mit Prednisolon, Azathioprin und Cyclosporin A. Abstosungsreaktionen wurden mit Prednisolon, bei Steroidresistenz mit ATG und/oder OKT3 behandelt.
Dielectric properties of lower aliphatic alcohols

Measurements of dielectric constants and loss in seven alcohols (from methyl to secondary butyl) have been made at frequencies from 15 c/s to 2 Mc/s over considerable ranges of temperature to extreme values of −150°C and 110°C. Also, solutions of water in ethyl and iso-propyl alcohols and of methyl with n-propyl alcohol have been studied.
Computational Investigation of the Interplay of Substrate Positioning and Reactivity in Catechol O-Methyltransferase.

Catechol O-methyltransferase (COMT) is a SAM- and Mg2+-dependent methyltransferase that regulates neurotransmitters through methylation. Simulations and experiments have identified divergent catecholamine substrate orientations in the COMT active site: molecular dynamics simulations have favored a monodentate coordination of catecholate substrates to the active site Mg2+, and crystal structures instead preserve bidentate coordination along with short (2.65 A) methyl donor-acceptor distances. We carry out longer dynamics (up to 350 ns) to quantify interconversion between bidentate and monodentate binding poses. We provide a systematic determination of the relative free energy of the monodentate and bidentate structures in order to identify whether structural differences alter the nature of the methyl transfer mechanism and source of enzymatic rate enhancement. We demonstrate that the bidentate and monodentate binding modes are close in energy but separated by a 7 kcal/mol free energy barrier. Analysis of interactions in the two binding modes reveals that the driving force for monodentate catecholate orientations in classical molecular dynamics simulations is derived from stronger electrostatic stabilization afforded by alternate Mg2+ coordination with strongly charged active site carboxylates. Mixed semi-empirical-classical (SQM/MM) substrate C-O distances (2.7 A) for the bidentate case are in excellent agreement with COMT X-ray crystal structures, as long as charge transfer between the substrates, Mg2+, and surrounding ligands is permitted. SQM/MM free energy barriers for methyl transfer from bidentate and monodentate catecholate configurations are comparable at around 21–22 kcal/mol, in good agreement with experiment (18–19 kcal/mol). Overall, the work suggests that both binding poses are viable for methyl transfer, and accurate descriptions of charge transfer and electrostatics are needed to provide balanced relative barriers when multiple binding poses are accessible, for example in other transferases.
de Quervain's thyroiditis: A review of experience with surgery

Abstract Background de Quervain's thyroiditis is an inflammatory condition of the thyroid mostly treated medically, rarely requiring surgical treatment. We intend to review the surgical experience with de Quervain's thyroiditis at a tertiary cancer center over a period of 22 years. Methods A retrospective review of medical records from 1992 to 2014 at a tertiary cancer center was performed and all patients with a histopathological diagnosis of de Quervain's thyroiditis were included. Results Ten patients with a histopathological diagnosis of de Quervain's thyroiditis were included in the study. One patient in the study presented with dysphagia due to the goiter. The remaining patients presented with thyroid nodules. None presented with typical symptoms of the disease. Seven of the ten patients that had been evaluated for a goiter at an outside facility underwent fine needle aspiration cytology. Of the seven patients, one patient was suspected to have medullary carcinoma of the thyroid, two had follicular neoplasia, and the others had indeterminate nodules. Eight of the ten patients underwent surgery for suspected malignancy, with eight receiving a total thyroidectomy and two patients getting a thyroid lobectomy with isthmusectomy. Two patients had an abnormally hard gland to palpate during surgery with the others not having any suspicious findings. Seven of the ten of the patients had lymph node sampling from level 6 and all were benign on final pathology. The mean duration of post-operative follow-up was 15 months. There was no morbidity associated with surgery in any of these patients with eight of the ten patients requiring thyroid hormone replacement. None of the patients needed further neck surgery for thyroid disease. Conclusion de Quervain's thyroiditis is an inflammatory condition of the thyroid that is rarely treated surgically. However when presentation is atypical and the FNAC is inconclusive or is suspicious for a malignancy, patients receive surgery putting them at a risk for morbidity. Good clinical assessment with combined use of ultrasound with FNAC especially read by an experienced cytopathologist has the potential to reduce unnecessary operative intervention.
The Utility of Preoperative Frailty Assessment

The geriatric patient population represents an ever increasing proportion of a surgeon’s practice spectrum. With this comes the need to understand the factors largely impacting the geriatric surgical population. One of these factors is frailty. At first glance frailty appears as a simple concept. However, a review of the literature reveals a plethora of definitions, quantification endeavors, and theories attempting to delineate its principle attributes. Despite the variety of theories, the literature supports a strong link between frailty and poor surgical outcomes. While this link is strong, the exact utility of frailty in preoperative assessments is still being appreciated both in the general surgery setting and in its subspecialties. In this review we first discuss the background and defining attributes of frailty and their relation to concepts closely associated with frailty such as resilience, multi-morbidity, and accelerating factors of aging. Understanding the prominent defining features and close associations allows for a greater appreciation of frailty’s clinical impact on the geriatric perioperative surgical assessment. Ultimately, when including frailty in the geriatric surgical assessment its consideration allows for modification in the preoperative, intraoperative, and postoperative setting with the overall goal of improving surgical outcomes in the geriatric population.
Effect of aphasia on acute stroke outcomes.

Objective: To determine the independent effects of aphasia on outcomes during acute stroke admission, controlling for total NIH Stroke Scale (NIHSS) scores and loss of consciousness. Methods: Data from the Tulane Stroke Registry were used from July 2008 to December 2014 for patient demographics, NIHSS scores, length of stay (LOS), complications (sepsis, deep vein thrombosis), and discharge modified Rankin Scale (mRS) score. Aphasia was defined as a score >1 on question 9 on the NIHSS on admission and hemiparesis as >1 on questions 5 or 6. Results: Among 1,847 patients, 866 (46%) had aphasia on admission. Adjusting for NIHSS score and inpatient complications, those with aphasia had a 1.22 day longer LOS than those without aphasia, whereas those with hemiparesis (n = 1,225) did not have any increased LOS compared to those without hemiparesis. Those with aphasia had greater odds of having a complication (odds ratio [OR] 1.44, confidence interval [CI] 1.07–1.93, p = 0.0174) than those without aphasia, which was equivalent to those having hemiparesis (OR 1.47, CI 1.09–1.99, p = 0.0137). Controlling for NIHSS scores, aphasia patients had higher odds of discharge mRS 3–6 (OR 1.42 vs 1.15). Conclusion: Aphasia is independently associated with increased LOS and complications during the acute stroke admission, adding $2.16 billion annually to US acute stroke care. The presence of aphasia was more likely to produce a poor functional outcome than hemiparesis. These data suggest that further research is necessary to determine whether establishing adaptive communication skills can mitigate its consequences in the acute stroke setting.
Abstraction and generalization in statistical learning: implications for the relationship between semantic types and episodic tokens

Statistical approaches to emergent knowledge have tended to focus on the process by which experience of individual episodes accumulates into generalizable experience across episodes. However, there is a seemingly opposite, but equally critical, process that such experience affords: the process by which, from a space of types (e.g. onions-a semantic class that develops through exposure to individual episodes involving individual onions), we can perceive or create, on-the-fly, a specific token (a specific onion, perhaps one that is chopped) in the absence of any prior perceptual experience with that specific token. This article reviews a selection of statistical learning studies that lead to the speculation that this process-the generation, on the basis of semantic memory, of a novel episodic representation-is itself an instance of a statistical, in fact associative, process. The article concludes that the same processes that enable statistical abstraction across individual episodes to form semantic memories also enable the generation, from those semantic memories, of representations that correspond to individual tokens, and of novel episodic facts about those tokens. Statistical learning is a window onto these deeper processes that underpin cognition.This article is part of the themed issue 'New frontiers for statistical learning in the cognitive sciences'.
Extraversion as a moderator for resilience factors among gay men

ABSTRACTThe present study examined the moderating role of extraversion on the relationship between depressive symptoms and the resilience factors of social support and emotional openness (the ability to accept and process one's emotion) among gay men. Extraversion, social support, and emotional openness were all associated with lower depressive symptoms. Extraversion did not moderate the relationship between social support and depressive symptoms among gay men. Extraversion moderated the relationship between emotional openness and depressive symptoms, such that emotional openness was associated with fewer depressive symptoms, particularly among gay men with a lower level of extraversion. Clinical implications are discussed.
Systematic Review of Racial/Ethnic Outcome Disparities in Home Health Care:

Introduction: Though extensive evidence demonstrates that U.S. minority patients suffer health care disparities, the incidence of disparities among the 3.3 million adult patients receiving skilled ...
How You Can Organize a GRA

(1955). How You Can Organize a GRA. Journal of Health, Physical Education, Recreation: Vol. 26, No. 4, pp. 19-54.
Use of multiplex PCR based molecular diagnostics in diagnosis of suspected CNS infections in tertiary care setting—A retrospective study

Abstract Objectives CNS infections like meningitis and encephalitis pose enormous healthcare challenges due to mortality, sequelae and socioeconomic burden. In tertiary setting, clinical, microbiological, cytological and radiological investigations are not distinctive enough for diagnosing microbial etiology. Molecular diagnostics is filling this gap. We evaluated the clinical impact of a commercially available multiplex molecular diagnostic system − SES for diagnosing suspected CNS infections. Patients and methods This study was conducted in our tertiary level Neurology ICU. 110 patients admitted during Nov-2010 to April-2014 were included. CSF samples of patients clinically suspected of having CNS infections were subjected to routine investigation in our laboratory and SES test at XCyton Diagnostics. We studied the impact of SES in diagnosis of CNS infections and its efficacy in helping therapeutic management. Results SES showed detection rate of 42.18% and clinical specificity of 100%. It had 10 times higher detection rate than conventional tests. Streptococcus pneumoniae and Mycobacterium tuberculosis were two top bacterial pathogens. VZV was most detected viral pathogen. SES results elicited changes in therapy in both positive and negative cases. We observed superior patient outcomes as measured by GCS scale. 75% and 82.14% of the patients positive and negative on SES respectively, recovered fully. Conclusion Detecting causative organism and ruling out infectious etiology remain the most critical aspect for management and prognosis of patients with suspected CNS infections. In this study, we observed higher detection rate of pathogens, target specific escalation and evidence based de-escalation of antimicrobials using SES. Institution of appropriate therapy helped reduce unnecessary use of antimicrobials.
Non-steroidal anti-inflammatory drugs in the oncological surgical population: beneficial or harmful? A systematic review of the literature

Abstract Background Non-steroidal anti-inflammatory drugs (NSAIDs) are effective analgesic drugs. Recent studies have indicated a potential beneficial effect on long-term survival outcomes after cancer surgery but a negative impact on anastomotic leaks. The objective of this study was to objectively assess the implications of the perioperative NSAIDs use on anastomotic leaks and cancer recurrence. Methods We searched PubMed, MEDLINE, Embase and Cochrane Library for publications up to mid-January 2017. Randomized controlled trials (RCTs) and observational studies in adults undergoing cancer surgery were included for quality assessment. We excluded animal studies, in vitro experiments and case reports. The selected sudies were graded using the Jadad score or Newcastle–Ottawa scale for RCTs and observational retrospective studies, respectively. Results The systematic review identified 25 trials that explored the impact of NSAIDs on anastomotic leaks and 16 trials that assessed the association between perioperative NSAIDs and cancer recurrence. Meta-analyses were not performed because of high heterogeneity and low quality of the included studies. Conclusions The literature is not conclusive on whether the use of NSAIDs is associated with anastomotic leaks after gastrointestinal cancer surgery. Also, the current evidence is equivocal regarding the effects of short-term NSAIDs on cancer recurrence after major cancer surgery. Three RCTs are being conducted to assess the impact of NSAIDs on cancer recurrence. There are no registered RCTs that are testing the hypothesis of whether the perioperative use of NSAIDs increases the rate of anastomotic leaks.
Limits and Hurdles to Continued CMOS Scaling

Abstract Limits or hurdles to scaling past 10 nm are considered. Limits are categorized into different groups: practical and engineering limits such as the cost of fabricators is one; the other is the need for a new lithographic process, such as extreme UV, and perhaps X-Ray or E-beam. These are two practical and basic “limits.” Scientific limits include various leakage currents in transistors with diminishing dimensions: limits to gate thickness, which are approaching 1 nm; contact pitch, which will challenge lithography. Device design also limits scaling. The positions of source-gate-drains have recently been changed to provide an advantage in vertical gates, for instance. Doping and electrical parameters such as drive voltage and threshold voltage limit scaling; leakage currents are on the rise and are a cause for concern. Some questions regarding thermodynamic limits, induced instabilities, and noise immunity have been raised. Dopant fluctuations at an atomic scale give rise to Vt variation. These are contributors to difficulties in signal control and stability of the device and memory. In the interconnect region, limits arise from increasing current density as the cross-section of the current carrying Cu lines decreases and the power and signal density increases. Higher current densities, together with increased metal layers, now exceeding nine layers of metal, give rise to greater heat generation and combine to increase electromigration failures. As the number of transistors increases, the heat output density from the chip also increases. Greater demands will be placed on device cooling. These various limits are discussed. Ongoing efforts to go beyond these limits are considered.
On the Inverse Gamma as a Survival Distribution

This paper presents properties of the inverse gamma distribution and how it can be used as a survival distribution. A result is included that shows that the inverse gamma distribution always has an upside-down bathtub (UBT) shaped hazard function, thus, adding to the limited number of available distributions with this property. A review of the utility of UBT distributions is provided as well. Probabilistic properties are presented first, followed by statistical properties to demonstrate its usefulness as a survival distribution. As the inverse gamma distribution is discussed in a limited and sporadic fashion in the literature, a summary of its properties is provided in an appendix.
The Uterine Corpus

During the reproductive years, the size and weight of a normal uterus vary according to parity. Nulliparous uteri weigh 40 to 100 g and measure about 8 cm in length, 5 cm in width at the fundus, and 2.5 cm in anteroposterior thickness. Muciparous uteri weigh up to 250 g and measure 12 cm × 5–7 cm × 3.5 cm.
Development of a gender-sensitive and recovery-oriented intervention for women with serious mental illness.

Objective A pilot study was conducted to develop and provide a formative evaluation of a group intervention for women with serious mental illness, Women's Empowerment and Recovery-Oriented Care (WE-ROC). Method Ten women with serious mental illness were recruited from a mental health center to take part in the pilot study. Several measures were utilized to assess prepost changes in recovery and empowerment and to elicit participant feedback. Results Results reflected a significant increase in recovery scores as well as empowerment scores. High attendance rates as well as satisfaction and effectiveness scores provided potential support for feasibility and acceptability of the study, respectively. Content analysis of qualitative feedback suggests positive impacts of group, particularly with regard to peer support and self-esteem. Conclusions and implications for practice Future implementation, refinement, and evaluation of the intervention can include a waitlist control group, additional postintervention assessment, and larger sample size. (PsycINFO Database Record (c) 2019 APA, all rights reserved).
Multifactorial Examination of Caregiver Burden in a National Sample of Family and Unpaid Caregivers

OBJECTIVES To examine factors associated with caregiver burden from a multifactorial perspective by examining caregiver and care recipient characteristics and a full range of caregiving tasks. DESIGN Nationally representative surveys of community‐dwelling older adults and their family caregivers residing in the United States. SETTING 2011 National Health and Aging Trends Study and National Study of Caregiving. PARTICIPANTS Community‐dwelling older adults and their family caregivers. MEASUREMENTS Caregiver burden, comprising emotional, physical, and financial difficulties associated with caregiving. RESULTS An estimated 14.9 million caregivers assisted 7.6 million care recipients. More than half of caregivers reported burden related to caregiving. In a multivariable regression model, caregivers who assisted with more activities of daily living and instrumental activities of daily living, health management tasks, and health system logistics were more likely to experience burden, as were female caregivers, adult child caregivers, caregivers in poor health, caregivers with anxiety symptoms, and those using respite care. Dementia was the only care recipient characteristic associated with burden. CONCLUSION Caregiver characteristics and provision of caregiving tasks determine caregiver burden more than care recipient characteristics. Absence of an association between type of a care recipient's chronic conditions and burden, except for dementia, suggests that the tasks that caregivers who assist older adults with a variety of health conditions undertake shape the experience of caregiving. J Am Geriatr Soc 67:277–283, 2019.
High-Throughput Screening for CYP21A1P-TNXA/TNXB Chimeric Genes Responsible for Ehlers-Danlos Syndrome in Patients with Congenital Adrenal Hyperplasia

Many patients with congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency have CAH-X syndrome, a connective tissue dysplasia consistent with hypermobility-type Ehlers-Danlos syndrome due to a contiguous gene deletion involving the adjacent CYP21A2 and TNXB genes. CAH-X syndrome is caused by carrying CYP21A1P-TNXA/TNXB chimeric genes [CAH-X chimera 1 (CH-1) and chimera 2 (CH-2)] on one or more alleles. Genetic analysis is cumbersome due to pseudogene interference. We developed a PCR-based CAH-X high-throughput screening method to assess the copy numbers of TNXB exons 35 and 40; this method is amenable to either real-time quantitative PCR or droplet digital PCR (ddPCR). The assay was validated in a cohort of 278 subjects from 146 unrelated CAH families. Results were confirmed by a validated Sanger sequencing platform. A total of 44 CAH-X–positive calls were made, with 42 (26 CH-1 and 16 CH-2) confirmed. The assay had 100% sensitivity (42 true/42 positives), 99.2% specificity (234 true/236 negatives), and an overall 99.3% accuracy (276/278). Calls made by real-time quantitative PCR and ddPCR were consistent (100%), and ddPCR offered easier data interpretation. The CAH-X prevalence was 15.6% (21/135 probands), higher than the previously estimated 8.5%, and was particularly high (29.2% or 21/72) in those with a 30-Kb deletion. This assay is suitable for high-throughput CAH-X screening, especially in subjects testing positive for CAH in neonatal screening.
Representativeness of a 63-Station Network for Depicting Climate Changes

Abstract Errors arising from the use of a sparse 63-station network in monitoring global and regional temperature changes are estimated by comparing results from a complete global data set from European Centre for Medium Range Forecasts analyses with those from the 63 gridpoints nearest the stations. For nine years of seasonal means, the correlations between the station network and the true values are generally quite high, but root-mean-square errors are also large outside of the tropics and are of the same order as the signal being sought. For the most part, this occurs because the variance of the 63-station network is too large so that although the overall low-frequency fluctuations are reasonably well depicted, their amplitude is too large. However, any missing data could greatly exacerbate errors arising from spatial sampling.
Mutation of CFAP57 causes primary ciliary dyskinesia by disrupting the asymmetric targeting of a subset of ciliary inner dynein arms

Abstract Primary ciliary dyskinesia (PCD) is characterized by chronic airway disease, male infertility, and randomization of the left/right body axis, and is caused by defects of motile cilia and sperm flagella. We screened a cohort of affected individuals that lack an obvious TEM structural phenotype for pathogenic variants using whole exome capture and next generation sequencing. The population sampling probability (PSAP) algorithm identified one subject with a homozygous nonsense variant [(c.1762C>T) p.(Arg588*) exon 11] in the uncharacterized CFAP57 gene. In normal human nasal epithelial cells, CFAP57 localizes throughout the ciliary axoneme. Analysis of cells from the PCD patient shows a loss of CFAP57, reduced beat frequency, and an alteration in the ciliary waveform. Knockdown of CFAP57 in human tracheobronchial epithelial cells (hTECs) recapitulates these findings. Phylogenetic analysis showed that CFAP57 is conserved in organisms that assemble motile cilia, and CFAP57 is allelic with the BOP2 gene identified previously in Chlamydomonas. Two independent, insertional fap57 Chlamydomonas mutant strains show reduced swimming velocity and altered waveforms. Tandem mass spectroscopy showed that CFAP57 is missing, and the “g” inner dyneins (DHC7 and DHC3) and the “d” inner dynein (DHC2) are reduced. Our data demonstrate that the FAP57 protein is required for the asymmetric assembly of inner dyneins on only a subset of the microtubule doublets, and this asymmetry is essential for the generation of an effective axonemal waveform. Together, our data identifies mutations in CFAP57 as a cause of PCD with a specific defect in the inner dynein arm assembly process. Significance Motile cilia are found throughout eukaryotic organisms and performs essential functions. Primary ciliary dyskinesia (PCD) is a rare disease that affects the function of motile cilia. By applying a novel population sampling probability algorithm (PSAP) that uses large population sequencing databases and pathogenicity prediction algorithms, we identified a variant in an uncharacterized gene, CFAP57. This is the first reported example of PCD caused by a mutation that affects only a subset of the inner dynein arms, which are needed to generate the waveform. CFAP57 identifies an address for specific dynein arms. These findings demonstrate the effectiveness of the PSAP algorithm, expand our understanding of the positioning of dynein arms, and identify mutations in CFAP57 as a cause of PCD.
Epidemiology of SFTS in Japan

Severe fever with thrombocytopenia syndrome (SFTS) is a novel tick-borne disease, which was first reported from China in 2009. Etiological pathogen was identified as SFTS virus (SFTSV), a novel phlebovirus in the family of Bunyaviridae in 2011. Since then, SFTS cases were reported from Korea and Japan.
Role of tagraxofusp in treating blastic plasmacytoid dendritic cell neoplasm (BPDCN).

Introduction: Advances and drug development in rare diseases, such as blastic plasmacytoid dendritic cell neoplasm (BPDCN), has historically been limited by small numbers of patients in the target ...
A Curriculum Design and Teaching Experience Created by and for Bioscience Postdoctoral Fellows in a Medical School.

Many medical school postdoctoral fellows (postdocs) lack training in curriculum design and student-centered instruction. A team of bioscience postdocs and a medical school curriculum assistant dean co-created an experience to fill this gap. Kern’s and Kirkpatrick’s frameworks were used for the design and evaluation, respectively, of both the postdoc experience and the undergraduate course they developed. Postdocs taught the course using student-centered methods, especially team-based learning and Just-in-Time Teaching. Following a successful pilot phase, this low resource postdoc experience and undergraduate course are regularly offered. Participating postdocs develop the knowledge, skills, and attitudes to effectively participate in medical school education.
Oregano essential oil addition in rice starch films and its effects on the chilled fish storage

Active packaging produced from biodegradable polymers and essential oil could have a great value to food industries. This study aimed to evaluate the effect of the addition of oregano essential oil (OEO) on rice starch films and its application as packaging for fish fillets. Several concentrations of OEO were added to the films, the film added with 4.5% OEO showed lower permeability to water vapor 3.7 g mm kPa−1 m−2 day−1, intermediate solubility of 24% and high tensile strength (4.4 MPa) while the standard film (without the addition of OEO) presented 8.8 g mm kPa−1 m−2 day−1, 25.8% and 2.2 MPa, respectively. Packed fish fillets with the active film showed an increase in its shelf life when compared to the standard film. Packaged fish fillets in OEO films showed greater resistance (13.4 N), less oxidation (1.65 mg malonaldehyde/kg of sample) and less microbiological growth 107 CFU/g in 6 days of storage, while packaged fish fillets in standard film showed lower resistance (10.4 N), higher oxidation (1.88 mg malonaldehyde/kg of sample) and higher microbiological growth 108 CFU/g. Thus, the active packaging developed had the capacity to increase the shelf life of a perishable product that has great interest of food industries.
Negative pressure increases microvascular perfusion during severe hemorrhagic shock.

Hemorrhagic shock (HS) is a severe life-threatening condition characterized by loss of blood volume and a lack of oxygen (O2) delivery to tissues. The objective of this study was to examine the impact of manipulating Starling forces in the microcirculation during HS to increase microvascular perfusion without restoring blood volume or increasing O2 carrying capacity. To decrease interstitial tissue pressure, we developed a non-contact system to locally apply negative pressure and manipulate the pressure balance in capillaries, while allowing for visualization of the microcirculation. Golden Syrian hamsters were instrumented with dorsal window chambers and subjected to a controlled hemorrhaged of 50% of the animal's blood volume without any fluid resuscitation. A negative pressure chamber was attached to the dorsal window chamber and a constant negative pressure was applied. Hemodynamic parameters (including microvascular diameter, blood flow, and functional capillary density [FCD]) were measured before and during the four hours following the hemorrhage, with and without applied negative pressure. Blood flow significantly increased in arterioles during negative pressure. The increase in flow through arterioles also improved microvascular perfusion as reflected by increased FCD. These results indicate that negative pressure increases flow in the microcirculation when fluid resuscitation is not available, thus restoring blood flow, oxygen delivery, and preventing the accumulation of metabolic waste. Applying negative pressure might allow for control of microvascular blood flow and oxygen delivery to specific tissue areas.
Proofs of the Main Results

Here the proofs of the main results are provided, modulo some more technical auxiliary parts, which are delegated to Chap. 5.
Antiretroviral drug exposure in urethral and glans surface sampling of the penis.

BACKGROUND HIV exposure to penile tissues provides a risk of acquisition among men, yet studies evaluating penile antiretroviral (ARV) drug distribution have been lacking. We measured ARVs on urethral and glans surface swabs collected following a dose of tenofovir alafenamide, emtricitabine, elvitegravir, darunavir and cobicistat. METHODS Thirty-five HIV-negative male participants provided urethral swabs, glans swabs, rectal swabs, blood and urine up to 96 h following a single dose of tenofovir alafenamide/emtricitabine/elvitegravir/cobicistat and darunavir. ARVs were measured by liquid chromatography-mass spectrometry with a lower limit of detection (LOD) of 1 ng/swab for swabs and 10 ng/mL for plasma and urine. Concentrations are reported as median and range. RESULTS Urethral swab emtricitabine and darunavir concentrations peaked at 4 h for emtricitabine (36 ng/swab; 3-307 ng/swab) and 8 h for darunavir (25 ng/swab; 2-52 ng/swab). Glans swab emtricitabine and darunavir concentrations peaked 24 h after dosing (emtricitabine 14 ng/swab, <LOD-328 ng/swab; darunavir 6 ng/swab, <LOD-149 ng/swab). Estimated peak urethral secretion emtricitabine and darunavir concentrations are between 10 and 20 μg/mL, similar to rectal secretions, 4-fold greater than in plasma, but 2-fold lower than in urine. Tenofovir and elvitegravir were detected on less than 20% of urethral or glans swabs collected within 24 h of dosing. CONCLUSIONS We document ARV dosing in the urethra and on the glans surface with high drug concentrations noted for emtricitabine and darunavir and lower tenofovir and elvitegravir concentrations. Data suggest a potential protective role of urethral emtricitabine or darunavir against penile HIV acquisition.
Alpha-Synuclein Preformed Fibrils Induce Cellular Senescence in Parkinson's Disease Models.

Emerging evidence indicates that cellular senescence could be a critical inducing factor for aging-associated neurodegenerative disorders. However, the involvement of cellular senescence remains unclear in Parkinson’s disease (PD). To determine this, we assessed the effects of α-synuclein preformed fibrils (α-syn PFF) or 1-methyl-4-phenylpyridinium (MPP+) on changes in cellular senescence markers, employing α-syn PFF treated-dopaminergic N27 cells, primary cortical neurons, astrocytes and microglia and α-syn PFF-injected mouse brain tissues, as well as human PD patient brains. Our results demonstrate that α-syn PFF-induced toxicity reduces the levels of Lamin B1 and HMGB1, both established markers of cellular senescence, in correlation with an increase in the levels of p21, a cell cycle-arrester and senescence marker, in both reactive astrocytes and microglia in mouse brains. Using Western blot and immunohistochemistry, we found these cellular senescence markers in reactive astrocytes as indicated by enlarged cell bodies within GFAP-positive cells and Iba1-positive activated microglia in α-syn PFF injected mouse brains. These results indicate that PFF-induced pathology could lead to astrocyte and/or microglia senescence in PD brains, which may contribute to neuropathology in this model. Targeting senescent cells using senolytics could therefore constitute a viable therapeutic option for the treatment of PD.
NOTCH-mediated ex vivo expansion of human hematopoietic stem and progenitor cells by culture under hypoxia.

Summary Activation of NOTCH signaling in human hematopoietic stem/progenitor cells (HSPCs) by treatment with an engineered Delta-like ligand (DELTA1ext-IgG [DXI]) has enabled ex vivo expansion of short-term HSPCs, but the effect on long-term repopulating hematopoietic stem cells (LTR-HSCs) remains uncertain. Here, we demonstrate that ex vivo culture of human adult HSPCs with DXI under low oxygen tension limits ER stress in LTR-HSCs and lineage-committed progenitors compared with normoxic cultures. A distinct HSC gene signature was upregulated in cells cultured with DXI in hypoxia and, after 21 days of culture, the frequency of LTR-HSCs increased 4.9-fold relative to uncultured cells and 4.2-fold compared with the normoxia + DXI group. NOTCH and hypoxia pathways intersected to maintain undifferentiated phenotypes in cultured HSPCs. Our work underscores the importance of mitigating ER stress perturbations to preserve functional LTR-HSCs in extended cultures and offers a clinically feasible platform for the expansion of human HSPCs.
A maximum likelihood approach towards aggregating partial orders

In many of the possible applications as well as the theoretical models of computational social choice, the agents' preferences are represented as partial orders. In this paper, we extend the maximum likelihood approach for defining "optimal" voting rules to this setting. We consider distributions in which the pairwise comparisons/incomparabilities between alternatives are drawn i.i.d. We call such models pairwise-independent models and show that they correspond to a class of voting rules that we call pairwise scoring rules. This generalizes rules such as Kemeny and Borda. Moreover, we show that Borda is the only pairwise scoring rule that satisfies neutrality, when the outcome space is the set of all alternatives. We then study which voting rules defined for linear orders can be extended to partial orders via our MLE model. We show that any weakly neutral outcome scoring rule (including any ranking/candidate scoring rule) based on the weighted majority graph can be represented as the MLE of a weakly neutral pairwise-independent model. Therefore, all such rules admit natural extensions to profiles of partial orders. Finally, we propose a specific MLE model πk for generating a set of k winning alternatives, and study the computational complexity of winner determination for the MLE of πk.
Dust in the Wind: Long Range Transport of Dust in the Atmosphere and Its Implications for Global Public and Ecosystem Health

Movement of soil particles in atmospheres is a normal planetary process. Images of Martian dust devils (wind-spouts) and dust storms captured by NASA's Pathfinder have demonstrated the significant role that storm activity plays in creating the red atmospheric haze of Mars. On Earth, desert soils moving in the atmosphere are responsible for the orange hues in brilliant sunrises and sunsets. In severe dust storm events, millions of tons of soil may be moved across great expanses of land and ocean. An emerging scientific interest in the process of soil transport in the Earth's atmosphere is in the field of public and ecosystem health. This article will address the benefits and the potential hazards associated with exposure to particle fallout as clouds of desert dust traverse the globe.
Social Impact Project Finance: An Innovative and Sustainable Infrastructure Financing Framework☆

Abstract The purpose of this article is to propose a framework of Social Impact Project Finance (SIPF) for financing infrastructure projects. In the framework, public sector commits to pay performance-based yield for improved services, which in turn motivate private investor to better construct and manage infrastructure assets. By embedding social impact performance criteria, SIPF has an endogenous incentive mechanism that can align perspectives of public and private sectors, while traditional project finance lacks. SIPF can also play a critical role in achieving sustainable infrastructure, because all three components of sustainability (social, environmental and economic) can be easily embedded as impact factors in the framework. In addition, it could be well customized for governments globally to address their own problems, such as carbon emission or congestion reduction. Private investor can also benefit from higher yield, liquidity, and tax break. With this innovative interdisciplinary initiation of impact finance and project finance, there will be significant opportunities to not only create a new format of impact-based project delivery methods, but also show us a prospective way to securitize and deliver public services under clear supervision in the future.