bluuebunny/crossref_metadata_2025 huggingface dataset:
Potential hemo-biological identification markers to the left displaced abomasum in dairy cows
Authors: Song Yuxiang , Loor Juan J , Zhao Chenchen , Huang Dan , Du Xiliang , Li Xiaobing , Wang Zhe , Liu Guowen , Li Xinwei
Published: December 2020

Background

Left displaced abomasum (LDA) occurs at high frequency in the early postpartum period and can affect production performance of dairy cows. Clinical diagnosis of LDA is usually done by abdominal auscultation and percussion. The purpose of this study was to explore the potential applicability of blood biomarkers for early warning and diagnosis of LDA in dairy cows.

Results

Twenty early postpartum healthy cows and thirty early postpartum LDA cows of similar parity were used. A receiver operating characteristic curve (ROC) method was used to analyze the sensitivity of hematological biomarkers to LDA including energy balance metabolic biomarkers, liver/kidney function biomarkers, and minerals. A cut-off point was defined for each of the selected hematological biomarkers deemed sensitive markers of LDA. Compared with healthy cows, body condition score (BCS), dry matter intake (DMI) and milk production were lower in LDA cows. Among energy metabolism markers, serum non-esterified fatty acid (NEFA), β-hydroxybutyric acid (BHBA), insulin (INS), and revised quantitative insulin sensitivity check index (RQUICKI) levels were lower while serum glucagon (GC) was greater in LDA cows. Among the liver/kidney function biomarkers, activities of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), γ-glutamyl transpeptidase (GGT), lactate dehydrogenase (LDH), the ratio of AST/ALT and levels of total bilirubin (TBIL), direct bilirubin (DBIL), indirect bilirubin (IBIL), albumin (ALB), blood urea nitrogen (BUN), creatinine, and total protein (TP) were greater in LDA cows. Among minerals analyzed, serum Cl, Ca, and K were lower in LDA cows. After ROC analysis, it was determined that serum Ca, INS, RQUICKI, ALT, GGT, and creatinine are potential indicators for early warning and diagnosis of LDA for early postpartum dairy cows.

Conclusions

Dairy cows with LDA were under severe negative energy balance (NEB), had signs of liver damage and potentially lower insulin sensitivity. A combination of multi-hematological biomarkers including Ca, INS, RQUICKI, ALT, GGT and creatinine has the potential to help identify cows at risk of LDA in the early postpartum period.
Role of human milk banks amid COVID 19: perspective from a milk bank in India
Authors: Bhasin Maheshwar , Nangia Sushma , Goel Srishti
Published: December 2020

The COVID-19 pandemic has had a significant impact on the operation of donor human milk banks in various countries such as China, Italy and India. It is understandable that this impact on operations of donor human milk might hamper the capability of these milk banks to provide sufficient pasteurized donor milk to neonates who need it. Contrary to developed world, predominant donors in developing nations are mothers of hospitalised neonates who have a relatively long period of hospital stay. This longer maternal hospital stay enhances the feasibility of milk donation by providing mothers with access to breast pumps to express their milk. Any excess milk a mother expresses which is above the needs of their own infant can be voluntarily donated. This physical proximity of milk banks to donors may help continuation of human milk donation in developing nations during the pandemic. Nevertheless, protocols need to be implemented to i) ensure the microbiological quality of the milk collected and ii) consider steps to mitigate potential consequences related to the possibility of the donor being an asymptomatic carrier of COVID-19. We present the procedural modifications implemented at the Comprehensive Lactation Management Centre at Lady Hardinge Medical College in India to promote breastfeeding and human milk donation during the pandemic which comply with International and National guidelines. This commentary provides a perspective from a milk bank in India which might differ from the perspective of the international donor human milk banking societies.
Effect of toe exercises and toe grip strength on the treatment of primary metatarsalgia
Authors: Amaha Kentaro , Arimoto Tatsuya , Kitamura Nobuto
Published: December 2020

Background

The relationship of metatarsalgia and toe function is poorly understood. We investigated the efficacy of toe exercises for the treatment of metatarsalgia.

Methods

Forty-one (56 feet) metatarsalgia patients (mean age ± SD: 63.4 ± 10.6) underwent toe strength measurement. We recorded pre- and post-treatment VAS score, AOFAS score, marble pickup, single-leg standing time (SLST), and compared in two subgroups to evaluate impact of disease duration on treatment outcome.

Results

Post treatment, toe plantarflexion strength improved (all p < 0.01); VAS scores decreased (p < 0.01); AOFAS scores, marble pickup, and SLST improved (all p < 0.01). Patients symptomatic for > 1 year had significantly lower changes in VAS scores (p < 0.01). Multivariate analysis showed patients with longer disease duration, and larger body mass index had significantly lower improvement in VAS scores (p = 0.029 and p = 0.036, respectively). Device consistency assessed by ICC was excellent (0.89–0.97).

Conclusion

Toe function and metatarsalgia are improved by toe exercises, suggesting that they are closely related.
First record of non-mineralized cephalopod jaws and arm hooks from the latest Cretaceous of Eurytania, Greece
Authors: Klug Christian , Davesne Donald , Fuchs Dirk , Argyriou Thodoris
Published: December 2020

Due to the lower fossilization potential of chitin, non-mineralized cephalopod jaws and arm hooks are much more rarely preserved as fossils than the calcitic lower jaws of ammonites or the calcitized jaw apparatuses of nautilids. Here, we report such non-mineralized fossil jaws and arm hooks from pelagic marly limestones of continental Greece. Two of the specimens lie on the same slab and are assigned to the Ammonitina; they represent upper jaws of the aptychus type, which is corroborated by finds of aptychi. Additionally, one intermediate type and one anaptychus type are documented here. The morphology of all ammonite jaws suggest a desmoceratoid affinity. The other jaws are identified as coleoid jaws. They share the overall U-shape and proportions of the outer and inner lamellae with Jurassic lower jaws of Trachyteuthis (Teudopseina). We also document the first belemnoid arm hooks from the Tethyan Maastrichtian. The fossils described here document the presence of a typical Mesozoic cephalopod assemblage until the end of the Cretaceous in the eastern Tethys.
IgE-binding to vicilin-like antimicrobial peptides is associated with systemic reactions to macadamia nut
Authors: Ehlers Anna M. , Rohwer Stefanie , Otten Henny G. , Brix Bettina , Le Thuy-My , Suer Waltraud , Knulst André C.
Published: December 2020

Background

Macadamia nut can induce fatal allergic reactions and changes in dietary habits will raise their consumption in industrialised countries. Until now diagnosis of macadamia nut allergy by sIgE solely relies on the macadamia nut extract, but single components are lacking.

Methods

Macadamia nut proteins recognised by IgE from 2 macadamia nut extract positive sera were identified by mass spectrometry (vicilin-like antimicrobial peptides: VLAP). Sensitisation to macadamia nut extract and heterologously expressed isoform VLAP-2–3 was evaluated in 82 nut allergic (NA) and 27 tolerant (NT) patients (no tree nut allergy reported) comprehending 10 macadamia nut allergic (MA) and 18 explicitly reported macadamia nut tolerant patients (MT), using line blots. Co-sensitisation to additional VLAP isoforms and other vicilins was evaluated in 8 MA, 12 MT and 14 NA patients sensitised to VLAP-2–3. Functional properties were determined by indirect basophil activation.

Results

Even though proteins recognised by IgE were identified as VLAP-2–1, 2–2 and 2–3, only peptides specifically belonging to VLAP-2–3 were detected by mass spectrometry. The macadamia nut extract was recognised by 33% of NA patients (27/82) including 3 MA patients and 26% of NT patients (7/27, 3 MT). Similarly, 29% of NA (24/82) patients showed partly strong sIgE-binding to VLAP-2–3 including 3 MA patients with systemic reactions to macadamia nut. Contrary, VLAP-2–3 was recognised by only 2 NT (1 MT) patients (7%) with very low sIgE titres. Simultaneous recognition of the isoforms VLAP-2–1 and 2–2 was observed in all patients positive for VLAP-2–3 with partly reduced sIgE titres in 59% of these patients. Additionally, all three VLAP isoforms were able to repeatedly induce BAT reactivity upon sensitisation with a MA serum.

Conclusion

VLAP proteins are the first described macadamia nut components with serological and functional allergenic properties and they are associated with systemic reactions to macadamia nut.
Disordered eating behaviors in youths with type 1 diabetes during COVID-19 lockdown: an exploratory study
Authors: Troncone Alda , Chianese Antonietta , Zanfardino Angela , Cascella Crescenzo , Piscopo Alessia , Borriello Anna , Rollato Serena , Casaburo Francesca , Testa Veronica , Iafusco Dario
Published: December 2020

Background

Recent research indicates that patients with type 1 diabetes (T1D) are at higher risk for disordered eating behaviors (DEBs) than their peers without diabetes. The present study aimed to explore the prevalence of DEBs in a sample of Italian children and adolescents with T1D and in matched-pair healthy controls during the COVID-19 lockdown.

Methods

In a cross-sectional study, 138 children and adolescents with T1D (aged 8.01–19.11 years, 65 boys) attending a Southern Italian diabetic service and 276 age- and gender-matched healthy peers voluntarily completed an online survey about eating behaviors (ChEAT and EAT-26), anthropometric characteristics, and clinical characteristics.

Results

8.69% (N = 12) of participants with T1D and 13.4% (N = 37) of controls had ChEAT/EAT-26 scores indicating presence of DEBs, with no differences between patients—whether children (total ChEAT score F(1, 157) = .104, p = .748) or adolescents (total EAT-26 score F(1, 255) = .135, p = .731)—and healthy peers. zBMI values were lower than those measured in the latest diabetes visit (p < .0001), while HbA1c values remained unchanged (p = .110). In both groups, adolescents had lower Oral Control scores than children (T1D: F(1, 138) = 20.411, p < .0001, η2 = .132, controls: F(1, 276) = 18.271, p < .0001, η2 = .063); additionally, gender (female) and age were found to be significant predictors of several ChEAT/EAT-26 scores.

Conclusions

This exploratory study suggested that children and adolescents with T1D did not experience more DEB symptoms during the COVID-19 lockdown compared to healthy controls. Results revealed DEBs as more of a female adolescent developmental issue rather than a result of the challenges of living with a chronic illness under quarantine measures. Possible effects of parental pressure on their children’s eating behaviors in the context of home confinement and of using a non-diabetes-specific measure to assess DEBs are discussed.
Integrating students’ perspectives about online learning: a hierarchy of factors
Authors: Van Wart Montgomery , Ni Anna , Medina Pamela , Canelon Jesus , Kordrostami Melika , Zhang Jing , Liu Yu
Published: December 2020

This article reports on a large-scale (n = 987), exploratory factor analysis study incorporating various concepts identified in the literature as critical success factors for online learning from the students’ perspective, and then determines their hierarchical significance. Seven factors--Basic Online Modality, Instructional Support, Teaching Presence, Cognitive Presence, Online Social Comfort, Online Interactive Modality, and Social Presence--were identified as significant and reliable. Regression analysis indicates the minimal factors for enrollment in future classes—when students consider convenience and scheduling—were Basic Online Modality, Cognitive Presence, and Online Social Comfort. Students who accepted or embraced online courses on their own merits wanted a minimum of Basic Online Modality, Teaching Presence, Cognitive Presence, Online Social Comfort, and Social Presence. Students, who preferred face-to-face classes and demanded a comparable experience, valued Online Interactive Modality and Instructional Support more highly. Recommendations for online course design, policy, and future research are provided.
Estimation of pollution indices and hazard evaluation from trace elements concentration in coastal sediments of Kerala, Southwest Coast of India
Authors: Vineethkumar V. , Sayooj V. V. , Shimod K. P. , Prakash V.
Published: December 2020

Background

The environment is always subjected to exposure from different natural and anthropogenic sources of trace elements. The excessive intake of these trace elements may become toxic and cause health disorders to the people when the concentration exceeds certain threshold limits. The measurement of trace elements concentration in general and toxic trace elements concentration in particular is important for the assessment and prediction of risk to the environment and public. Distribution of trace elements in various environmental matrices depends on the nature of the element itself and the site-specific characteristics such as type of the matrices and its physicochemical parameters. In view of these aspects, an attempt is made to assess the concentration of trace elements and pollution indices in the sediment samples collected from the coastal belt of Kerala and possible conclusions were drawn.

Results

The results of pollution indices clearly indicate the moderate level of trace elements contamination in the coastal belts of Kerala. Significant correlations were observed between the concentration of trace elements and physicochemical parameters of the sediments.

Conclusion

Most of the trace elements enrichment in the coastal belt is due the crustal materials or natural weathering process and atmospheric deposition. The investigation revealed the sources of most of the elements present in the coastal belt of Kerala are lithogenic such as weathering and atmospheric deposition.
Outcomes of Indeterminate Thyroid Nodules Managed Nonoperatively after Molecular Testing
Authors: Zhu Catherine Y , Donangelo Ines , Gupta Deepashree , Nguyen Dalena T , Ochoa Joana E , Yeh Michael W , Livhits Masha J
Published: December 2020

Context

Molecular testing to refine the diagnosis of cytologically indeterminate thyroid nodules has become increasingly popular, but data on long-term durability of test results and the rate of delayed operation are limited.

Objective

Determine the delayed rate of surgical resection in indeterminate nodules with benign/negative molecular testing and the risk of false-negative molecular test results.

Design

Prospective follow-up of the Gene Expression Classifier vs Targeted Next-Generation Sequencing in the Management of Indeterminate Thyroid Nodules randomized controlled trial comparing the diagnostic test performance of Afirma Gene Expression Classifier and ThyroSeq v2.

Setting

University of California, Los Angeles.

Participants

Patients who underwent thyroid biopsy with indeterminate (Bethesda III/IV) cytology (April 2016 to July 2017).

Intervention

Ultrasound surveillance.

Main Outcome Measure

False-negative rate of molecular testing.

Results

Of 95 indeterminate nodules with negative/benign molecular test results, 12 nodules underwent immediate resection (11 benign nodules, 1 noninvasive follicular thyroid neoplasm nodule with papillary-like nuclear features). Nonoperative management was pursued for 83 (87.4%) nodules. The median surveillance was 26.7 months. Ten nodules were resected during surveillance and malignancy was identified in 4 nodules (overall false-negative rate of 5.8%). In the 4 malignant nodules that underwent delayed operation, surgery was prompted by sonographic changes during surveillance.

Conclusions

The majority of indeterminate nodules with negative molecular testing have a stable clinical course over 3 years of follow-up, but our finding of a 6% false-negative rate highlights the importance of continuing sonographic surveillance. Long-term studies are needed to determine the optimal length of follow-up.
Induction of Functional Hypothalamus and Pituitary Tissues From Pluripotent Stem Cells for Regenerative Medicine
Authors: Kano Mayuko , Suga Hidetaka , Arima Hiroshi
Published: December 2020

The hypothalamus and pituitary have been identified to play essential roles in maintaining homeostasis. Various diseases can disrupt the functions of these systems, which can often result in serious lifelong symptoms. The current treatment for hypopituitarism involves hormone replacement therapy. However, exogenous drug administration cannot mimic the physiological changes that are a result of hormone requirements. Therefore, patients are at a high risk of severe hormone deficiency, including adrenal crisis.

Pluripotent stem cells (PSCs) self-proliferate and differentiate into all types of cells. The generation of endocrine tissues from PSCs has been considered as another new treatment for hypopituitarism. Our colleagues established a 3-dimensional (3D) culture method for embryonic stem cells (ESCs). In this culture, the ESC-derived aggregates exhibit self-organization and spontaneous formation of highly ordered patterning. Recent results have shown that strict removal of exogenous patterning factors during early differentiation efficiently induces rostral hypothalamic progenitors from mouse ESCs. These hypothalamic progenitors generate vasopressinergic neurons, which release neuropeptides upon exogenous stimulation.

Subsequently, we reported adenohypophysis tissue self-formation in 3D cultures of mouse ESCs. The ESCs were found to differentiate into both nonneural oral ectoderm and hypothalamic neuroectoderm in adjacent layers. Interactions between the 2 tissues appear to be critically important for in vitro induction of a Rathke’s pouch-like developing embryo. Various endocrine cells were differentiated from nonneural ectoderm. The induced corticotrophs efficiently secreted adrenocorticotropic hormone when engrafted in vivo, which rescued hypopituitary hosts.

For future regenerative medicine, generation of hypothalamic and pituitary tissues from human PSCs is necessary. We and other groups succeeded in establishing a differentiation method with the use of human PSCs. Researchers could use these methods for models of human diseases to elucidate disease pathology or screen potential therapeutics.
iPSC-derived hepatocytes generated from NASH donors provide a valuable platform for disease modeling and drug discovery
Authors: Gurevich Igor , Burton Sarah A. , Munn Christie , Ohshima Makiko , Goedland Madelyn E. , Czysz Katherine , Rajesh Deepika
Published: December 2020

Non-alcoholic fatty liver disease (NAFLD) affects 30 to 40% of adults and 10% of children in the US. About 20% of people with NAFLD develop non-alcoholic steatohepatitis (NASH), which may lead to cirrhosis and liver cancer, and is projected to be a leading cause of liver transplantation in the near future. Human induced pluripotent stem cells (iPSC) from NASH patients are useful for generating a large number of hepatocytes for NASH modeling applications and identification of potential drug targets. We developed a novel defined in vitro differentiation process to generate cryopreservable hepatocytes using an iPSC panel of NASH donors and apparently healthy normal (AHN) controls. iPSC-derived hepatocytes displayed stage specific phenotypic markers, hepatocyte morphology, with bile canaliculi. Importantly, both fresh and cryopreserved Definitive Endoderm and Hepatoblasts successfully differentiated to pure and functional hepatocytes with increased CYP3A4 activity in response to rifampicin and lipid accumulation upon fatty acid (FA) treatment. End stage hepatocytes integrated into three dimensional liver organoids and demonstrated increased levels of albumin secretion compared to aggregates consisting of hepatocytes alone. End stage hepatocytes derived from NASH donors demonstrated spontaneous lipidosis without fatty acid supplementation, recapitulating a feature of NASH hepatocytes in vivo. Cryopreserved hepatocytes generated by this protocol across multiple donors will provide a critical cell source to facilitate the fundamental understanding of NAFLD/NASH biology and potential high throughput screening applications for preclinical evaluation of therapeutic targets.
Strain specific differences in muscle Ca2+ transport and mitochondrial electron transport proteins between FVB/N and C57BL/6J mice
Authors: Singh Sushant , Periasamy Muthu , Bal Naresh C.
Published: December 2020

Genetically engineered mouse models have been used to determine the role of sarcolipin (SLN) in muscle. However, few studies had difficulty in detecting SLN in FBV/N mice and questioned its relevance to muscle metabolism. It is known that genetic alteration of proteins in different inbred mice strains produce dissimilar functional outcome. Therefore, here we compared the expression of SLN and key proteins involved in Ca2+-handling and mitochondrial metabolism between FVB/N and C57BL/6J mouse strains. Data suggests that, SLN expression is less abundant in the skeletal muscles of FVB/N mice compared to C57BL/6J strain. The expression of Ca2+-transporters in the mitochondrial membranes, were also lower in FVB/N compared to C57BL/6J. Similarly the electron transport proteins in the mitochondria were less abundant in FVB/N mice which may contribute to differences in energy metabolism. Future studies using different mouse strains should take these differences into account while interpreting their data.
Case Report: Simultaneously diagnosed gastric adenocarcinoma and pernicious anemia – a classic association
Authors: Kamran Syed , Dilling Mattias K. , Parker Nathaniel A. , Alderson Joel , Tofteland Nathan D. , Truong Quoc V.
Published: December 2020

Primary gastric cancer remains one of the most prevalent malignancies worldwide. Often patients remain asymptomatic until it is detected at an advanced stage with a poor prognosis. Thus, it’s characteristically difficult to initially diagnose until it becomes late stage, at which point prognosis becomes poor. Pernicious anemia is a classic risk factor for the development of primary gastric cancer, but is uncommonly seen in clinical practice. Over time, patients who produce the autoantibodies to intrinsic factor that cause pernicious anemia typically will present initially with clinically significant megaloblastic anemia and peripheral neuropathy. However, patients can also present with more nonspecific signs and symptoms. Thus, clinicians should remain vigilant as circulating anti-intrinsic factor antibodies only worsen the disease over time and increase the risk of developing primary gastric cancer. This report not only presents the rare concurrent diagnosis of pernicious anemia and gastric cancer, but also aims to increase clinical awareness of these two conditions’ classic association because early diagnosis and treatment significantly impacts morbidity and mortality.
Review of the nutritional composition, medicinal, phytochemical and pharmacological properties of Citrus reticulata Blanco (Rutaceae)
Authors: Musara Collen , Aladejana Elizabeth Bosede , Mudyiwa Silas Mufambi
Published: December 2020

Citrus reticulata Blanco is a moderately-sized fruit tree widely used as herbal medicine worldwide. The nutritional composition, medicinal uses, phytochemistry and pharmacological properties of C. reticulata were critically reviewed in the current study. The literature linked to C. reticulata properties was obtained from multiple internet sources including Elsevier, Google Scholar, SciFinder, Web of Science, Pubmed, BMC, Science Direct, and Scopus. Ethnopharmacological research identified antioxidants such as vitamin C, carotenoids and phenolic compounds, also a source of sugars, organic acids, amino acids, pectins, minerals and volatile organic compounds as components of C. reticulata. As a medicinal plant, C. reticulata is used for the treatment of dyspepsia, gastro-intestinal distension, cough with profuse phlegm, hiccup and vomiting. The crude extracts of C. reticulata fruits have depicted anti-inflammatory, anticholesterolemic, analgesic, antiasthmatic, antiscorbutic, antiseptic, antitussive, carminative, expectorant, stomachic. With more people becoming nutrition-conscious, there has been an increase in the demand for the use of citrus fruits and their by-products as traditional medicines for conventional healthcare in developing countries.
Celebrating the legacy of Mary Seacole
Authors: Eftekhari Helen
Published: December 2020

The Year of the Nurse has not only coincided with the global COVID-19 pandemic, but also the growing momentum of the Black Lives Matter movement. BANCC president-elect Helen Eftekhari highlights the legacy of British-Jamaican nurse Mary Seacole to modern nursing and the vital contributions made to the profession by black, Asian and minority ethnic nurses today.
Hand tendon injuries
Authors: Campbell E , Pillai S , Vamadeva SV , Pahal GS
Published: December 2020

This article provides a comprehensive overview of hand tendon injuries. It has been tailored towards healthcare professionals who will be the first to assess these injuries and instigate appropriate management. It discusses the essential hand anatomy to be aware of, how to assess tendon injuries, their initial management and also the definitive surgical interventions used, if required. Rehabilitation techniques are also discussed, as this is also key to good functional outcomes. Missed injuries, or delay in their diagnosis and referral to specialist hand surgeons, can cause a large amount of morbidity for patients and therefore it is important that they are picked up in a timely manner.
COVID‐19 and Independent Abortion Providers: Findings from a Rapid‐Response Survey
Authors: Roberts Sarah C.M. , Schroeder Rosalyn , Joffe Carole
Published: December 2020

CONTEXT

The ways in which the COVID‐19 pandemic has affected abortion providers and abortion care, and the strategies clinics are adopting to navigate the pandemic, have not been well documented.

METHODS

In April–May 2020, representatives from 103 independent abortion clinics (i.e., those not affiliated with Planned Parenthood) completed a survey that included close‐ended questions about how the pandemic, the public health response, and designations of abortion as a nonessential service had affected their clinic, as well as open‐ended questions about the pandemic's impact. Analyses were primarily descriptive but included an exploration of regional variation.

RESULTS

All U.S. regions were represented in the sample. At 51% of clinics, clinicians or staff had been unable to work because of the pandemic or public health responses. Temporary closures were more common among clinics in the South (35%) and Midwest (21%) than in the Northeast and West (5% each). More than half of clinics had canceled or postponed nonabortion services (e.g., general gynecologic care); cancelation or postponement of abortion services was less common (25–38%, depending on type) and again especially prevalent in the South and Midwest. Respondents reported the pandemic had had numerous effects on their clinics, including disrupting their workforce, clinic flow and work practices; increasing expenses; and reducing revenues. State laws (including designations of abortion as nonessential) had exacerbated these difficulties.

CONCLUSIONS

Although independent abortion clinics have faced considerable challenges from the pandemic, most continued to provide abortion care. Despite this resiliency, additional support may be needed to ensure sustainability of these clinics.
Compact integration of GaN-based photonic chip with microfluidics system
Authors: An Xiaoshuai , Chen Liang , Li Jing , Li Kwai Hei
Published: December 2020

This Letter reports a demonstration of integrating a tiny GaN-based photonic chip with a PDMS microfluidics system. The photonic chip containing InGaN/GaN quantum wells is responsible for light emission and photodetection and fabricated through standard microfabrication techniques. The PDMS-enclosed chip is formed adjacent to the fluidic channel and operates in reflection mode, enabling the optical signals coupled into and out of the fluidic channel without the aid of external optics. The luminescence and photo-detecting properties are thoroughly characterized, confirming that the chip is capable of tracking the continuously flowing microdroplets with the changes of absorbance, length, and flow rate. The novel, to the best of our knowledge, photonic integration presented in this Letter is a significant step forward in the development of compact, miniature, and self-contained on-chip sensing systems, which are of great value in portable lab-on-a-chip applications.
3D printing of silica glass through a multiphoton polymerization process
Authors: Doualle Thomas , André Jean-Claude , Gallais Laurent
Published: December 2020

We introduce a laser-based process relying on multiphoton-induced polymerization to produce complex three-dimensional (3D) glass parts. A focused, intense laser beam is used to polymerize a transparent resin, loaded with additives and silica nanoparticles, at the wavelength of the laser beam through nonlinear absorption processes. The object is created directly in the volume, overcoming the limitation of the layer-by-layer process. The process enables the production of silica parts with consecutive debinding and sintering processes. With bulk silica density and a resolution that depends on the laser spot size, 3D objects of centimetric dimensions are obtained.
Drug2ways: Reasoning over causal paths in biological networks for drug discovery
Authors: Rivas-Barragan Daniel , Mubeen Sarah , Guim Bernat Francesc , Hofmann-Apitius Martin , Domingo-Fernández Daniel
Published: December 2020

Elucidating the causal mechanisms responsible for disease can reveal potential therapeutic targets for pharmacological intervention and, accordingly, guide drug repositioning and discovery. In essence, the topology of a network can reveal the impact a drug candidate may have on a given biological state, leading the way for enhanced disease characterization and the design of advanced therapies. Network-based approaches, in particular, are highly suited for these purposes as they hold the capacity to identify the molecular mechanisms underlying disease. Here, we present drug2ways, a novel methodology that leverages multimodal causal networks for predicting drug candidates. Drug2ways implements an efficient algorithm which reasons over causal paths in large-scale biological networks to propose drug candidates for a given disease. We validate our approach using clinical trial information and demonstrate how drug2ways can be used for multiple applications to identify: i) single-target drug candidates, ii) candidates with polypharmacological properties that can optimize multiple targets, and iii) candidates for combination therapy. Finally, we make drug2ways available to the scientific community as a Python package that enables conducting these applications on multiple standard network formats.
In situ observations on the dentition and oral cavity of the Neanderthal skeleton from Altamura (Italy)
Authors: Riga Alessandro , Boggioni Marco , Papini Andrea , Buzi Costantino , Profico Antonio , Di Vincenzo Fabio , Marchi Damiano , Moggi-Cecchi Jacopo , Manzi Giorgio
Published: December 2020

The Neanderthal specimen from Lamalunga Cave, near Altamura (Apulia, Italy), was discovered during a speleological survey in 1993. The specimen is one of the most complete fossil hominins in Europe and its state of preservation is exceptional, although it is stuck in calcareous concretions and the bones are mostly covered by calcite depositions. Nevertheless, it is possible to carry out some observations on craniodental features that have not previously been described. In this work, we present an account of the oral cavity, made possible by the use of a videoscope, which allowed us to reach some hidden parts of the mandible and palate. This is the first detailed overview of the teeth and maxillary bones of the Neanderthal skeleton from Altamura. The dentition is almost complete. However, two teeth (upper right P3 and upper left M1) were lostante mortemand four teeth (lower right I1 and P3 and lower left I1 and I2) were lost most probablypost mortem. Dental wear is marked. The erupted M3s and the inversion of the compensating curve of Wilson in the M1s and M2s but not in the M3s suggest that the individual is fully adult, but not old. Although most of the teeth have their roots exposed for several millimeters, the periodontal bone appears to be in good condition overall, except in correspondence of the twoante-mortemtooth losses. X-rays of the anterior teeth show a periapical lesion, probably linked to the advanced dental wear. We also observed a weak expression of taurodontism in the posterior dentition and the presence of a retromolar space, features consistent with an attribution to the Neanderthal hypodigm; this attribution is also supported by aspects of the cranial morphology, the morphometric analysis of the scapula and preliminary mtDNA data. There is also a well-developed palatine torus, to the best of our knowledge a feature not previously described in Neanderthals.
Measuring event concentration in empirical networks with different types of degree distributions
Authors: Campos Juan , Finke Jorge
Published: December 2020

Measuring event concentration often involves identifying clusters of events at various scales of resolution and across different regions. In the context of a city, for example, clusters may be characterized by the proximity of events in the metric space. However, events may also occur over urban structures such as public transportation and infrastructure systems, which are naturally represented as networks. Our work provides a theoretical framework to determine whether events distributed over a set of interconnected nodes are concentrated on a particular subset. Our main analysis shows how the proposed or any other measure of event concentration on a network must explicitly take into account its degree distribution. We apply the framework to measure event concentration (i) on a street network (i.e., approximated as a regular network where events represent criminal activities); and (ii) on a social network (i.e., a power law network where events represent users who are dissatisfied after purchasing the same product).
Shade is the most important factor limiting growth of a woody range expander
Authors: Ward David
Published: December 2020

The expansion of woody plants into grasslands and old fields is often ascribed to fire suppression and heavy grazing, especially by domestic livestock. However, it is also recognized that nutrient availability and interspecific competition with grasses and other woody plants play a role in certain habitats. I examined potential factors causing range- and niche expansion by the eastern redcedarJuniperus virginiana, the most widespread conifer in the eastern United States, in multifactorial experiments in a greenhouse. Historical records suggest that the eastern redcedar is a pioneer forest species, and may be replaced as the forest increases in tree density due to shading. Another possible factor that affects its distribution may be nutrient availability, which is higher in old fields and other disturbed lands than in undisturbed habitats. In its historic range, eastern redcedars are particularly abundant on limestone outcrops, often termed ‘cedar barrens’. However, the higher abundance on limestone could be due to reduced interspecific competition rather than a preference for high pH substrates. I manipulated shade, fertilization, lime, and interspecific competition with a common dominant tree, the post oakQuercus stellata. In a separate experiment, I manipulated fire and grass competition. I measured growth rates (height and diameter) and above- and belowground biomass at the end of both experiments. I also measured total non-structural carbohydrates and nitrogen in these plants. Shade was the most important factor limiting the growth rates and biomass of eastern redcedars. I also found that there were significant declines in nitrogen and non-structural carbohydrates when shaded. These results are consistent with the notion that the eastern redcedar is a pioneer forest species, and that shade is the reason that these redcedars are replaced by other tree species. In the second experiment, I found that a single fire had a negative effect on young trees. There was no significant effect of competition with grass, perhaps because the competitive effect was shading by grasses and not nutrient depletion. Overall, the effects of shade were far more apparent than the effects of fire.
Maternal exposure to sulfonamides and adverse pregnancy outcomes: A systematic review and meta-analysis
Authors: Li Peixuan , Qin Xiaoyun , Tao Fangbiao , Huang Kun
Published: December 2020

Background

Sulfonamides are widely used to treat infectious diseases during pregnancy. However, the safety of maternal exposure to sulfonamides is controversial. This study aims to systematically review the available studies and examine the effect of maternal sulfonamides use on adverse pregnancy outcomes.

Methods

We searched PubMed, Science Direct, Web of Science, ClinicalTrials.gov, CNKI and Wanfang Database (in Chinese). The meta-analysis used random effects model or fixed effects model to obtain the total odds ratio (OR) for each outcome through Stata11.0 software. Study on the relationship between sulfonamide exposure during pregnancy and adverse pregnancy outcomes. The study design covered randomized controlled trials, cohort studies and case-control studies. The study protocol was registered in PROSPERO with protocol number CRD42020178687.

Results

A total of 10 studies, and 1096350 participants were included for systematic review. Maternal exposure to sulfonamides was found to be possibly associated with increased risk of congenital malformations (OR = 1.21, 95% CI 1.07–1.37). The use of sulfonamides in the first trimester of pregnancy and during the entire pregnancy might be associated with congenital malformations.

Conclusions

Maternal exposure to sulfonamides may be associated with offspring’ s congenital malformations. Prescription of sulfonamides for pregnant women is suggested to be carefully censored.
Genetic factors contributing to extensive variability of sex-specific hepatic gene expression in Diversity Outbred mice
Authors: Melia Tisha , Waxman David J.
Published: December 2020

Sex-specific transcription characterizes hundreds of genes in mouse liver, many implicated in sex-differential drug and lipid metabolism and disease susceptibility. While the regulation of liver sex differences by growth hormone-activated STAT5 is well established, little is known about autosomal genetic factors regulating the sex-specific liver transcriptome. Here we show, using genotyping and expression data from a large population of Diversity Outbred mice, that genetic factors work in tandem with growth hormone to control the individual variability of hundreds of sex-biased genes, including many long non-coding RNA genes. Significant associations between single nucleotide polymorphisms and sex-specific gene expression were identified as expression quantitative trait loci (eQTLs), many of which showed strong sex-dependent associations. Remarkably, autosomal genetic modifiers of sex-specific genes were found to account for more than 200 instances of gain or loss of sex-specificity across eight Diversity Outbred mouse founder strains. Sex-biased STAT5 binding sites and open chromatin regions with strain-specific variants were significantly enriched at eQTL regions regulating correspondingly sex-specific genes, supporting the proposed functional regulatory nature of the eQTL regions identified. Binding of the male-biased, growth hormone-regulated repressor BCL6 was most highly enriched attrans-eQTL regions controlling female-specific genes. Co-regulated gene clusters defined by overlapping eQTLs included sets of highly correlated genes from different chromosomes, further supportingtrans-eQTL action. These findings elucidate how an unexpectedly large number of autosomal factors work in tandem with growth hormone signaling pathways to regulate the individual variability associated with sex differences in liver metabolism and disease.
An examination of validity and reliability of the Parental Stress Scale in a population based sample of Norwegian parents
Authors: Nærde Ane , Sommer Hukkelberg Silje
Published: December 2020

The parental stress scale (PSS) is a widely used instrument that assesses stress related to child rearing. Even though several studies have investigated the construct validity and reliability of the PSS, no consensus has been reached regarding which and how many of the original eighteen items that should be included, or a robust factor structure with satisfactory reliability. The present study tested the psychometric properties of the Norwegian version of the PSS and used the advantages of complementary exploratory and confirmatory factor analyses to investigate the underlying factor structure of the PSS items. Data stem from a community sample of 1096 parents from five counties in Norway with a one-year-old child. The sample was randomly split (N = 553/543), and exploratory and confirmatory analyses were performed on each of the samples. Using predefined criteria for the selection of robust items, results revealed a two-dimensional structure (Parental stressors and Lack of rewards) across 13 PSS items, displaying satisfactory reliability. Network analyses revealed differential associations within item constellations and with covariates. Implications of the findings and study limitations are discussed.
A multicenter, randomized, open-label, controlled trial to evaluate the efficacy and tolerability of hydroxychloroquine and a retrospective study in adult patients with mild to moderate coronavirus disease 2019 (COVID-19)
Authors: Chen Cheng-Pin , Lin Yi-Chun , Chen Tsung-Chia , Tseng Ting-Yu , Wong Hon-Lai , Kuo Cheng-Yu , Lin Wu-Pu , Huang Sz-Rung , Wang Wei-Yao , Liao Jia-Hung , Liao Chung-Shin , Hung Yuan-Pin , Lin Tse-Hung , Chang Tz-Yan , Hsiao Chin-Fu , Huang Yi-Wen , Chung Wei-Sheng , Cheng Chien-Yu , Cheng Shu-Hsing ,   on behalf of the Taiwan HCQ Study Group
Published: December 2020

Objective

In this study, we evaluated the efficacy of hydroxychloroquine (HCQ) against coronavirus disease 2019 (COVID-19) via a randomized controlled trial (RCT) and a retrospective study.

Methods

Subjects admitted to 11 designated public hospitals in Taiwan between April 1 and May 31, 2020, with COVID-19 diagnosis confirmed by pharyngeal real-time RT-PCR for SARS-CoV-2, were randomized at a 2:1 ratio and stratified by mild or moderate illness. HCQ (400 mg twice for 1 d or HCQ 200 mg twice daily for 6 days) was administered. Both the study and control group received standard of care (SOC). Pharyngeal swabs and sputum were collected every other day. The proportion and time to negative viral PCR were assessed on day 14. In the retrospective study, medical records were reviewed for patients admitted before March 31, 2020.

Results

There were 33 and 37 cases in the RCT and retrospective study, respectively. In the RCT, the median times to negative rRT-PCR from randomization to hospital day 14 were 5 days (95% CI; 1, 9 days) and 10 days (95% CI; 2, 12 days) for the HCQ and SOC groups, respectively (p = 0.40). On day 14, 81.0% (17/21) and 75.0% (9/12) of the subjects in the HCQ and SOC groups, respectively, had undetected virus (p = 0.36). In the retrospective study, 12 (42.9%) in the HCQ group and 5 (55.6%) in the control group had negative rRT-PCR results on hospital day 14 (p = 0.70).

Conclusions

Neither study demonstrated that HCQ shortened viral shedding in mild to moderate COVID-19 subjects.
Social and child care provision in kinship networks: An agent-based model
Authors: Gostoli Umberto , Silverman Eric
Published: December 2020

Providing for the needs of the vulnerable is a critical component of social and health policy-making. In particular, caring for children and for vulnerable older people is vital to the wellbeing of millions of families throughout the world. In most developed countries, this care is provided through both formal and informal means, and is therefore governed by complex policies that interact in non-obvious ways with other areas of policy-making. In this paper we present an agent-based model of social and child care provision in the UK, in which agents can provide informal care or pay for private care for their relatives. Agents make care decisions based on numerous factors including their health status, employment, financial situation, and social and physical distance to those in need. Simulation results show that the model can produce plausible patterns of care need and availability, and therefore can provide an important aid to this complex area of policy-making. We conclude that the model’s use of kinship networks for distributing care and the explicit modelling of interactions between social care and child care will enable policy-makers to develop more informed policy interventions in these critical areas.

“The moral test of government is how it treats those who are in the dawn of life,the children;those who are in the twilight of life,the aged;and those in the shadows of life, the sick,the needy and the handicapped.”

— Hubert Humphrey Jr.