bluuebunny/crossref_metadata_2025 huggingface dataset:
Physical Conditioning Strategies for the Prevention of Concussion in Sport: a Scoping Review
Authors: Garnett Daniel , Patricios Jon , Cobbing Saul
Published: May 2021

Background

Concussion in sports has received a great deal of media attention and may result in short and longer-lasting symptoms, especially in adolescents. Although significant strides have been made in the identification and management of concussion, less is known about the primary prevention of this condition. The aims of this scoping review are to (1) summarize the current research of physical conditioning strategies to reduce or prevent concussion incidence in individuals participating in sport, especially adolescents, and (2) to identify gaps in the knowledge base. Our research question was what is known from the existing literature about physical preparation strategies to reduce or prevent concussion in adult and adolescent sports?

Methods

Three literature searches were conducted by information officers at two universities at six-month intervals, using five electronic databases (PubMed;WorldCat.org; Mendeley; EBSCOHost and Ovid MEDLINE). To increase the search range, subject experts were consulted and articles and reference lists were hand searched. A scoping review methodology identified eligible studies that analyzed physical preparation techniques on modifiable physical risk factors in athletes to reduce the incidence of concussion. The PRISMA-ScR checklist guided the reporting of the findings.

Results

A total of 1414 possible articles were identified, after duplicates removed, and articles analyzed against the inclusion and exclusion criteria, only 9 articles qualified for analysis. Two articles were found from studying reference lists. Thus, a total of 11 articles were included in the final evaluation for the purposes of this study. Data are reported from mostly adolescent subjects participating in nine different sports from three countries. Findings are presented with specific reference to previously recognized modifiable risk factors of concussion which include neck strength, neck size, cervical stiffness, type of sport, and pre-activity exercises.

Conclusions

There is limited research examining the physical preparation of athletes, especially in adolescents, to reduce or prevent concussion, and conflicting evidence in the few small sample studies that were identified. This scoping review identifies the research gap for a potentially vital modifiable risk factor, notably in the physical preparation of children and adolescents to reduce or prevent sports-related concussion.
Changes in physiotherapy students’ beliefs and attitudes about low back pain through pre-registration training
Authors: Christe Guillaume , Darlow Ben , Pichonnaz Claude
Published: May 2021

Background

Implementation of best-practice care for patients with low back pain (LBP) is an important issue. Physiotherapists’ who hold unhelpful beliefs are less likely to adhere to guidelines and may negatively influence their patients’ beliefs. Pre-registration education is critical in moving towards a biopsychosocial model of care. This study aimed to investigate the changes in 2nd year physiotherapy students’ beliefs about LBP after a module on spinal pain management and determine whether these changes were maintained at the end of academic training.

Methods

During three consecutive calendar years, this longitudinal cohort study assessed physiotherapy students’ beliefs with the Back Pain Attitudes Questionnaires (Back-PAQ) in their 1st year, before and after their 2nd year spinal management learning module, and at the end of academic training (3rd year). Unpaired t-tests were conducted to explore changes in Back-PAQ score.

Results

The mean response rate after the spinal management module was 90% (128/143 students). The mean (± SD) Back-PAQ score was 87.73 (± 14.21) before and 60.79 (± 11.44) after the module, representing a mean difference of − 26.95 (95%CI − 30.09 to − 23.80, p < 0.001). Beliefs were further improved at the end of 3rd year (− 7.16, 95%CI − 10.50 to − 3.81, p < 0.001).

Conclusions

A spinal management learning module considerably improved physiotherapy students’ beliefs about back pain. Specifically, unhelpful beliefs about the back being vulnerable and in need of protection were substantially decreased after the module. Improvements were maintained at the end of academic training one-year later. Future research should investigate whether modifying students’ beliefs leads to improved clinical practice in their first years of practice.
Effect of X-ray irradiation on the F1 generation of Sitophilus zeamais Motschulsky and the germination rate of maize grain
Authors: Bell-Gam Sobifagha Princess , Nwosu Luke Chinaru , Ileke Kayode David , Aguwa Uwaoma Otuodichinma
Published: May 2021

Background

The use of X-ray irradiation in the control of the maize weevil, Sitophilus zeamais Motschulsky (Coleoptera: Curculionidae) infesting stored maize was tested at 60, 70 and 80 KeV as part of the international concerted efforts to save maize production and enhance food security. Investigations were done in the laboratory at mean temperature and relative humidity of 29.2 °C and 75.7%, respectively using three varieties of maize. The possibility that X-ray irradiation can affect the viability of maize grains when planted after weevil control process was also evaluated in the laboratory. Standard methods were used to achieve the specific objectives, and X-ray machine snap constituted the exposure time for each dose.

Results

The results revealed 10% mortality of adult weevils after 24 h and 40% mortality after a period of 7 days. The result indicates moderate effect on mortality. Progressive increase in mortality was recorded as dose increased from 60 to 80 KeV. X-ray irradiation at the doses tested did not significantly (P > 0.05) restrict S. zeamais emergence from maize grains and did not also significantly protect grains against damage and flour production. There was no difference in the pattern of daily emergence of new progenies and pattern of accumulated emergence. The relationship between X-ray irradiation doses and weight of emerging progenies require more specific analysis. Absence of significant difference between the viability of irradiated grains and un-irradiated grains strongly suggests that X-ray irradiation did not adversely affect seed viability, and this gives irradiation technique an opportunity of higher acceptability in agriculture.

Conclusions

We recommend > 80 KeV of X-ray irradiation or its incorporation into integrated pest management system in order to achieve effective post-harvest control of the pest.
Predicting the geographic distribution habitats of Schizomyia buboniae (Diptera: Cecidomyiidae) and its host plant Deverra tortuosa (Apiaceae) in Egypt by using MaxEnt modeling
Authors: Kamel Mohamed , Bream Ahmed S. , Moursy Mohamed M. , Ragab Sanad H.
Published: May 2021

Background

In some localities of the Mediterranean coast and the Nile land region, the gall midgeSchizomyia buboniaeFrauenfeld, 1859 (Diptera: Cecidomyiidae) induce small barrel-shaped galls on the stem ofDeverra tortuosa(Desf.) DC. (Family: Apiaceae). Host plants interact with several insects in a different manner. The current work studies the interaction ofS. buboniaewithD. tortuosa. Furthermore, the present work predicted the distribution ofS. buboniaeand its host plantD. tortuosain Egypt by using MaxEnt modeling, in addition to the effect of elevation and vegetation cover on its distribution.

Results

The predominance ofS. buboniaeoccurred during late winter to spring. TheS. buboniaelarvae are occasionally attacked by endoparasitoids of the genusInostemma(Platygastridae). There was a significant positive correlation between the number of galls per plant and the plant cover within the study localities. Meanwhile, there was no significant correlation between the number of galls per plant and the altitude within the study localities. Also, the high temperature and altitude were the most important predictors for the habitat distribution ofS. buboniaeand its host plantD. tortuosa. The predicted distribution range size forS. buboniaeis less than the total predicted distribution range size forD. tortuosa.

Conclusions

The current study suggests that the gall inducer prefers large plants more than small ones. The present study suggests that the habitat distribution patterns ofS. buboniaeand its host plantD. tortuosain Egypt can be modeled using a small number of occurrence records together with environmental variable layers for the study area through the maximum entropy modeling technique.
Ultrasound-guided penile block for circumcision instead of anatomical landmark method in newborn babies
Authors: Yildirim Serap Aktas , Ozcan Hamiyet , Turkoz Ayda
Published: May 2021

Background

The primary objective of this study is to compare the effectiveness of the newborn’s penile block performed by the surgeon using the classical landmark method and the penile block performed by the anesthesiologist with ultrasound guidance.

Results

This prospective, single-blinded, randomized clinical study included a total of forty newborn babies scheduled to undergo elective circumcision. The babies were randomized into two treatment groups of ultrasound (US)-guided penile block (group I; n = 20) and classical landmark method dorsal penile nerve block (DPNB) (group II; n = 20) group. Face, Legs, Activity, Cry, Consolability (FLACC) score was used to determine the block efficacy and postoperative pain and analgesic requirements. Intraoperative and postoperative FLACC scores, intraoperative analgesic needs, discharge time, complications, first oral intake time, and parent’s satisfaction were also recorded.

FLACC scores were higher in group II than in group I during the intraoperative periods. Heart rate was higher in group II than in group I, at the incision, and during the procedure (P< 0.05). The number of patients requiring fentanyl was higher in group II than in group I (P< 0.01). FLACC scores were statistically higher in the landmark group at arrival in the PACU (P< 0.01) and after 30 min up to 2 h (P< 0.01). Parent’s satisfaction was significantly higher in US group (P< 0.01)

Conclusions

Intraoperative analgesic needs and pain scores are lower in newborn babies who performed penile block with ultrasound-guided compared to the landmark method.
Can trace element supplementations (Cu, Se, and Zn) enhance human immunity against COVID-19 and its new variants?
Authors: Nedjimi Bouzid
Published: May 2021

Background

Coronavirus-19 (SARS-CoV-2) is constantly changed through mutation, and new stains of this virus are detected throughout the world such as B.1.1.7 (UK), B.1.351 (South Africa), and P.1 (Brazil). These strains seem to be more easily transmissible than other variants, which may lead to more cases and more deaths. Currently, there are many vaccines for SARS-CoV-2 available in the market but without full clinical data beside. Despite the existence of these vaccines, the numbers of outpatients are still increasing in many countries around the world, and the reliability of these vaccines still remains elusive. It is well known that trace element deficiencies increase the individual susceptibility to immune dysfunction and lead to global health problem. In this context, improving the immune defense system to combats this pandemic is absolutely necessary. The purpose of this review is to establish the probable relation between trace elements supplementation and COVID-19.

Main body

Several clinical studies confirmed that Cu, Se, and Zn insufficiencies alter the immune system and increase the vulnerability to viral infections. Based on antiviral and anti-inflammatory effects of these micronutrients, it seems logical that dietary supplementations of these components might enhance human immune system and lower the graveness of COVID-19 infection.

Conclusion

Based on available data, we hypothesize that the clinical use of some essential trace element supplementations such as copper, selenium, and zinc might be a preventive and promising option to enhance human immunity against the new pandemic COVID-19 and its new strains.

Graphical abstract
The Telepsychiatry Operational Guidelines 2020 in India: a welcome step
Authors: Rina Kumari , Padhy Susanta Kumar , Chadda Rakesh Kumar
Published: May 2021

The release of the Telepsychiatry Operational Guidelines 2020 in India, during the COVID-19 pandemic, is a relief for both clinicians and patients. These guidelines embark on initiating and executing naive and recently started telepsychiatry services in India. The document is aligned with other ethical regulations, policies, laws and the 2020 Telemedicine Practice Guidelines in India. This paper discusses a few points about the broader applicability of the guideline for the benefit of humankind in the prevailing healthcare crisis. The guidelines may be extrapolated in policy-making for telepsychiatry services in other low- and middle-income countries sharing a similar socioeconomic, cultural and political milieu.
Impact of COVID-19 on Outcomes for Patients With Cervical Cancer in India
Authors: Gupta Nidhi , Chauhan Akashdeep Singh , Prinja Shankar , Pandey Awadhesh Kumar
Published: May 2021

PURPOSE

The COVID-19 pandemic has placed unprecedented demands on the health system. This led to delays in the initiation and completion of cancer treatment. We assessed the long-term health consequences because of the delay in diagnosis and treatment for cervical cancer due to COVID-19 in India.

METHODS

We used a Markov-model–based analysis assessing the lifetime health outcomes of the cohort of women population at risk from cervical cancer in India. The decrease in survival for those with the treatment interruption was calculated based on the number of days the treatment was extended beyond the standard duration. Furthermore, to model the impact of late diagnosis and delayed treatment initiation, the patients were assumed to have upstaged during the delay period, as per natural progression of disease.

RESULTS

We estimate 2.52% (n = 795) to 3.80% (n = 2,160) lifetime increase in the deaths caused by cervical cancer with treatment restrictions ranging from 9 weeks to 6 months, respectively, as compared to no delay. On the contrary, 88-238 deaths because of COVID-19 disease are estimated to be saved during this restriction period among the patients with cervical cancer. Overall, the excess mortality because of cervical cancer led to 18,159-53,626 life-years being lost and an increase of 16,808-50,035 disability-adjusted life-years.

CONCLUSION

Delays in diagnosis and treatment are likely to lead to more cervical cancer deaths as compared to COVID-19 mortality averted among the patients with cervical cancer. Health systems must reorganize in terms of priority setting for provision of care, starting with prioritizing the treatment of patients with early-stage cervical cancer, increasing use of teleconsultation, and strengthening the role of primary care physicians in provision of cancer care.
Association of a Lay Health Worker–Led Intervention on Goals of Care, Quality of Life, and Clinical Trial Participation Among Low-Income and Minority Adults With Cancer
Authors: Patel Manali I. , Khateeb Sana , Coker Tumaini
Published: May 2021

PURPOSE:

New approaches are needed to overcome low supportive care and clinical trial participation among low-income and minority adults with cancer. The objective of this project was to determine whether a lay health worker intervention was associated with improvements in supportive care and trial participation.

METHODS:

We conducted a quality improvement initiative in collaboration with a union organization. We enrolled union members newly diagnosed with cancer into a 6-month lay health worker–led intervention from October 15, 2016, to February 28, 2017. The primary outcome was goals of care. Secondary outcomes were health-related quality of life (HRQOL), health care use, and trial participation. All outcomes except HRQOL were compared with a cohort of union members diagnosed within the 6-month preintervention period.

RESULTS:

Sixty-six adults participated in the intervention group, and we identified 72 adults in the control group. Demographic characteristics were similar between groups. The mean age was 56.0 years; 47 (34%) were male, and 22 were White (16%). Within 6 months enrollment, more intervention group participants, as compared with the control, had clinician-documented goals of care (94% v 26%; P < .001) and participated in cancer clinical trials (72% v 22%; P < .001). At 4 months postenrollment, as compared with baseline, intervention participants experienced HRQOL improvements (mean difference, 3.98 points; standard deviation, 2.83; P < .001). Before death, more intervention group participants used palliative care and hospice than the control group.

CONCLUSION:

Lay health worker–led interventions may improve supportive care and clinical trial participation among low-income and minority populations with cancer.
Room temperature superconductivity dome at a Fano resonance in superlattices of wires
Authors: Vittoria Mazziotti Maria , Jarlborg Thomas , Bianconi Antonio , Valletta Antonio
Published: May 2021

Recently room temperature superconductivity with

degrees Celsius has been discovered in a pressurized complex ternary hydride, CSH
x
, which is a carbon- and hydrogen-doped H3S alloy. The nanoscale structure of H3S is a particular realization of the 1993 patent claim of superlattice of quantum wires for room temperature superconductors and the maximum T

C
occurs at the top of a superconducting dome. Here we focus on the electronic structure of materials showing nanoscale heterostructures at the atomic limit made of a superlattice of quantum wires like hole-doped cuprate perovskites, and organics focusing on A15 intermetallics and pressurized hydrides. We provide a perspective of the theory of room temperature multigap superconductivity in heterogeneous materials tuned at a shape resonance or Fano resonance in the superconducting gaps near a Lifshitz transition focusing on H3S where the maximum T

C
occurs where the multiband metal is tuned by pressure near a Lifshitz transition. Here the superconductivity dome of T

C
 vs. pressure is driven by both electron-phonon coupling and contact exchange interaction. We show that the T

C
amplification up to room temperature is driven by the Fano resonance between a superconducting gap in the anti-adiabatic regime and other gaps in the adiabatic regime. In these cases the T

C
amplification via contact exchange interaction is the missing term in conventional multiband BCS and anisotropic Migdal-Eliashberg theories including only Cooper pairing.
A Life Course Approach to the Relationship Between Fetal Growth and Hypothalamic-Pituitary-Adrenal Axis Function
Authors: Martin Wrivu N , Wang Carol A , Lye Stephen J , Matthews Stephen G , Reynolds Rebecca M , McLaughlin Carly E , Smith Roger , Pennell Craig E
Published: May 2021

Context

Human and animal studies suggest that hypothalamic-pituitary-adrenal axis (HPA-A) function may be programmed in utero; however, these findings are inconsistent. Given the powerful metabolic actions of cortisol, it is important to clarify the influence of early life on adult HPA-A function.

Objective

To determine the relationship between fetal growth and HPA-A stress response to a psychosocial stressor in young adults.

Design

Multigenerational, prospective cohort study (the Raine Study) conducted between 1989 and 1991.

Setting

King Edward Memorial Hospital, Perth, Western Australia, Australia.

Participants

A total of 917 participants aged 18 years from Gen2 of the Raine Study.

Main Outcome Measures

Measures of hypothalamic-pituitary-adrenal axis function before and after exposure to the Trier Social Stress Test.

Results

In fully adjusted models, an inverse linear relationship was observed between birthweight and plasma measures of (1) baseline cortisol (β = -0.90%, 95% CI: -1.73 to -0.07; P = 0.03); (2) peak cortisol (β = -0.78%, 95% CI -1.51 to -0.06; P = 0.03); (3) area under the curve with respect to ground (β = -0.89%, 95% CI -1.60 to -0.18; P = 0.01); and (4) adrenal sensitivity (β = -1.02, 95% CI: -1.85 to -0.18; P = 0.02). Similar results were demonstrated for percent optimal birthweight. No consistent quadratic relationships were identified. No associations were found between measures of fetal adiposity and HPA-A function at age 18 years, or fetal growth and HPA-A response pattern. Removal of anticipatory responders from the models substantially attenuated the observed relationships.

Conclusion

We observed an inverse linear relationship between fetal growth and HPA-A function at age 18 years. This differs from the inverse parabolic relationship (inverted U curve) reported in adults of advanced age. Altered adrenal sensitivity may underlie this relationship.
MRI-based Texture Analysis of Trabecular Bone for Opportunistic Screening of Skeletal Fragility
Authors: Zaworski Caroline , Cheah Jonathan , Koff Matthew F , Breighner Ryan , Lin Bin , Harrison Jonathan , Donnelly Eve , Stein Emily M
Published: May 2021

Context

Many individuals at high risk for osteoporosis and fragility fracture are never screened by traditional methods. Opportunistic use of imaging obtained for other clinical purposes is required to foster identification of these patients.

Objective

The aim of this pilot study was to evaluate texture features as a measure of bone fragility, by comparing clinically acquired magnetic resonance imaging (MRI) scans from individuals with and without a history of fragility fracture.

Methods

This study retrospectively investigated 100 subjects who had lumbar spine MRI performed at our institution. Cases (n = 50) were postmenopausal women with osteoporosis and a confirmed history of fragility fracture. Controls (n = 50) were age- and race-matched postmenopausal women with no known fracture history. Trabecular bone from the lumbar vertebrae was segmented to create regions of interest within which a gray level co-occurrence matrix was used to quantify the distribution and spatial organization of voxel intensity. Heterogeneity in the trabecular bone texture was assessed by several features, including contrast (variability), entropy (disorder), and angular second moment (homogeneity).

Results

Texture analysis revealed that trabecular bone was more heterogeneous in fracture patients. Specifically, fracture patients had greater texture variability (+76% contrast; P = 0.005), greater disorder (+10% entropy; P = 0.005), and less homogeneity (−50% angular second moment; P = 0.005) compared with controls.

Conclusions

MRI-based textural analysis of trabecular bone discriminated between patients with known osteoporotic fractures and controls. Further investigation is required to validate this promising methodology, which could greatly expand the number of patients screened for skeletal fragility.
G Protein–coupled Receptors in Radioiodine-refractory Thyroid Cancer in the Era of Precision Medicine
Authors: Suteau Valentine , Seegers Valérie , Munier Mathilde , Ben Boubaker Rym , Reyes Cécile , Gentien David , Wery Méline , Croué Anne , Illouz Frédéric , Hamy Antoine , Rodien Patrice , Briet Claire
Published: May 2021

Context

Radioiodine-refractory thyroid cancers have poor outcomes and limited therapeutic options (tyrosine kinase inhibitors) due to transient efficacy and toxicity of treatments. Therefore, combinatorial treatments with new therapeutic approaches are needed. Many studies link G protein–coupled receptors (GPCRs) to cancer cell biology.

Objective

To perform a specific atlas of GPCR expression in progressive and refractory thyroid cancer to identify potential targets among GPCRs aiming at drug repositioning.

Methods

We analyzed samples from tumor and normal thyroid tissues from 17 patients with refractory thyroid cancer (12 papillary thyroid cancers [PTCs] and 5 follicular thyroid cancers [FTCs]). We assessed GPCR mRNA expression using NanoString technology with a custom panel of 371 GPCRs. The data were compared with public repositories and pharmacological databases to identify eligible drugs. The analysis of prognostic value of genes was also performed with TCGA datasets.

Results

With our transcriptomic analysis, 4 receptors were found to be downregulated in FTC (VIPR1, ADGRL2/LPHN2, ADGRA3, and ADGRV1). In PTC, 24 receptors were deregulated, 7 of which were also identified by bioinformatics analyses of publicly available datasets on primary thyroid cancers (VIPR1, ADORA1, GPRC5B, P2RY8, GABBR2, CYSLTR2, and LPAR5). Among all the differentially expressed genes, 22 GPCRs are the target of approved drugs and some GPCRs are also associated with prognostic factors.

Discussion

For the first time, we performed GPCR mRNA expression profiling in progressive and refractory thyroid cancers. These findings provide an opportunity to identify potential therapeutic targets for drug repositioning and precision medicine in radioiodine-refractory thyroid cancer.
Early Impairment of Insulin Sensitivity, β-Cell Responsiveness, and Insulin Clearance in Youth with Stage 1 Type 1 Diabetes
Authors: Galderisi Alfonso , Moran Antoinette , Evans-Molina Carmella , Martino Mariangela , Santoro Nicola , Caprio Sonia , Cobelli Claudio
Published: May 2021

Context

Clinical onset of type 1 diabetes (Stage 3 T1D) is preceded by a presymptomatic phase characterized by multiple islet autoantibodies with normal glucose tolerance (Stage 1 T1D).

Objective

The aim was to explore the metabolic phenotypes of β-cell function and insulin sensitivity and clearance in normoglycemic youth with Stage 1 T1D and compare them with healthy nonrelated peers during a 3-hour oral glucose tolerance test (OGTT).

Methods

Twenty-eight lean youth, 14 with ≥2 islet autoantibodies (cases) and 14 healthy controls underwent a 3-hour 9-point OGTT with measurement of glucose, C-peptide, and insulin. The oral minimal model was used to quantitate β-cell responsiveness (φtotal) and insulin sensitivity (SI), allowing assessment of β-cell function by the disposition index (DI=φtotal×SI). Fasting insulin clearance (CL0) was calculated as the ratio between the fasting insulin secretion rate (ISR) and plasma insulin levels (ISR0/I0), while postload clearance (CL180) was estimated by the ratio of AUC of ISR over the plasma insulin AUC for the 3-hour OGTT (ISRAUC/IAUC). Participants with impaired fasting glucose, impaired glucose tolerance, or any OGTT glucose concentration ≥200 mg/dL were excluded.

Results

Cases (10.5 years [8, 15]) exhibited reduced DI (P < .001) due to a simultaneous reduction in both φtotal (P < 0.001) and SI (P = .008) compared with controls (11.5 years [10.4, 14.9]). CL0 and CL180 were lower in cases than in controls (P = .005 and P = .019).

Conclusion

Presymptomatic Stage 1 T1D in youth is associated with reduced insulin sensitivity and lower β-cell responsiveness, and the presence of blunted insulin clearance.
Dysgenesis and Dysfunction of the Pancreas and Pituitary Due toFOXA2Gene Defects
Authors: Kaygusuz Sare Betul , Arslan Ates Esra , Vignola Maria Lillina , Volkan Burcu , Geckinli Bilgen Bilge , Turan Serap , Bereket Abdullah , Gaston-Massuet Carles , Guran Tulay
Published: May 2021

Context

Developmental disorders of the pituitary gland leading to congenital hypopituitarism can either be isolated or associated with extrapituitary abnormalities (syndromic hypopituitarism). A large number of syndromic hypopituitarism cases are linked to mutations in transcription factors. The forkhead box A2 (FOXA2) is a transcription factor that plays a key role in the central nervous system, foregut, and pancreatic development.

Objective

This work aims to characterize 2 patients with syndromic hypopituitarism due to FOXA2 gene defects.

Results

We report a novel heterozygous nonsense c.616C > T(p.Q206X) variant that leads to a truncated protein that lacks part of the DNA-binding domain of FOXA2, resulting in impaired transcriptional activation of the glucose transporter type 2 (GLUT2)-luciferase reporter. The patient is the sixth patient described in the literature with a FOXA2 mutation, and the first patient exhibiting pancreatic hypoplasia. We also report a second patient with a novel de novo 8.53 Mb deletion of 20p11.2 that encompasses FOXA2, who developed diabetes mellitus that responded to sulfonylurea treatment.

Conclusion

Our 2 cases broaden the molecular and clinical spectrum of FOXA2-related disease, reporting the first nonsense mutation and the first case of pancreatic dysgenesis.
Noncanonical Thyroid Hormone Receptor α Action Mediates Arterial Vasodilation
Authors: Geist Daniela , Hönes G Sebastian , Gassen Janina , Kerp Helena , Kleinbongard Petra , Heusch Gerd , Führer Dagmar , Moeller Lars C
Published: May 2021

Context

Hypothyroidism impairs cardiovascular health and contributes to endothelial dysfunction with reduced vasodilation. How 3,5,3′-triiodothyronine (T3) and its receptors are involved in the regulation of vasomotion is not yet fully understood. In general, thyroid hormone receptors (TRs) either influence gene expression (canonical action) or rapidly activate intracellular signaling pathways (noncanonical action).

Objective

Here we aimed to characterize the T3 action underlying the mechanism of arterial vasodilation and blood pressure (BP) regulation.

Methods

Mesenteric arteries were isolated from male rats, wild-type (WT) mice, TRα knockout (TRα 0) mice, and from knockin mice with a mutation in the DNA-binding domain (TRα GS). In this mutant, DNA binding and thus canonical action is abrogated while noncanonical signaling is preserved. In a wire myograph system, the isolated vessels were preconstricted with norepinephrine. The response to T3 was measured, and the resulting vasodilation (Δ force [mN]) was normalized to maximum contraction with norepinephrine and expressed as percentage vasodilation after maximal preconstriction with norepinephrine (%NE). Isolated vessels were treated with T3 (1 × 10–15 to 1 × 10–5 mol/L) alone and in combination with the endothelial nitric oxide–synthase (eNOS) inhibitor L-NG-nitroarginine methyl ester (L-NAME) or the phosphatidylinositol 3-kinase (PI3K) inhibitor wortmannin. The endothelium was removed to determine the contribution of T3 to endothelium-dependent vasodilation. The physiological relevance of T3-induced vasodilation was determined by in vivo arterial BP measurements in male and female mice.

Results

T3 treatment induced vasodilation of mesenteric arteries from WT mice within 2 minutes (by 21.5 ± 1.7%NE). This effect was absent in arteries from TRα 0 mice (by 5.3 ± 0.6%NE, P < .001 vs WT) but preserved in TRα GS arteries (by 17.2 ± 1.1%NE, not significant vs WT). Inhibition of either eNOS or PI3K reduced T3-mediated vasodilation from 52.7 ± 4.5%NE to 28.5 ± 4.1%NE and 22.7 ± 2.9%NE, respectively. Removal of the endothelium abolished the T3-mediated vasodilation in rat mesenteric arteries (by 36.7 ± 5.4%NE vs 3.5 ± 6.2%NE). In vivo, T3 injection led to a rapid decrease of arterial BP in WT (by 13.9 ± 1.9 mm Hg) and TRα GS mice (by 12.4 ± 1.9 mm Hg), but not in TRα 0 mice (by 4.1 ± 1.9 mm Hg).

Conclusion

These results demonstrate that T3 acting through noncanonical TRα action affects cardiovascular physiology by inducing endothelium-dependent vasodilation within minutes via PI3K and eNOS activation.
Stable establishment of organ polarity occurs several plastochrons before primordium outgrowth in Arabidopsis
Authors: Zhao Feng , Traas Jan
Published: May 2021

In many species, leaves are initiated at the flanks of shoot meristems. Subsequent growth usually occurs mainly in the plane of the leaf blade, which leads to the formation of a bifacial leaf with dorsoventral identities. In a classical set of surgical experiments in potato meristems, Sussex provided evidence that dorsoventrality depends on a signal emanating from the meristem center. Although these results could be reproduced in tomato, this concept has been debated. We revisited these experiments in Arabidopsis, in which a range of markers are available to target the precise site of ablation. Using specific markers for organ founder cells and dorsoventral identity, we were unable to perturb the polarity of leaves and sepals long before organ outgrowth. Although results in Solanaceae suggested that dorsoventral patterning was unstable during early development, we found that, in Arabidopsis, the local information contained within and around the primordium is able to withstand major invasive perturbations, long before polarity is fully established.
Visual perception and camouflage response to 3D backgrounds and cast shadows in the European cuttlefish, Sepia officinalis
Authors: El Nagar Aliya , Osorio Daniel , Zylinski Sarah , Sait Steven M.
Published: May 2021

To conceal themselves on the seafloor, European cuttlefish, Sepia officinalis, express a large repertoire of body patterns. Scenes with 3D relief are especially challenging because it is not possible either to directly recover visual depth from the 2D retinal image or for the cuttlefish to alter its body shape to resemble nearby objects. Here, we characterised cuttlefish camouflage responses to 3D relief, and to cast shadows, which are complementary depth cues. Animals were recorded in the presence of cylindrical objects of fixed (15 mm) diameter, but varying in height, greyscale and strength of cast shadows, and to corresponding 2D pictorial images. With the cylinders, the cuttlefish expressed a ‘3D’ body pattern, which is distinct from previously described Uniform, Mottle and Disruptive camouflage patterns. This pattern was insensitive to variation in object height, contrast and cast shadow, except when shadows were most pronounced, in which case the body patterns resembled those used on the 2D backgrounds. This suggests that stationary cast shadows are not used as visual depth cues by cuttlefish, and that rather than directly matching the 2D retinal image, the camouflage response is a two-stage process whereby the animal first classifies the physical environment and then selects an appropriate pattern. Each type of pattern is triggered by specific cues that may compete, allowing the animal to select the most suitable camouflage, so the camouflage response is categorical rather than continuously variable. These findings give unique insight into how an invertebrate senses its visual environment to generate the body pattern response.
How head shape and substrate particle size affect fossorial locomotion in lizards
Authors: Bergmann Philip J. , Berry David S.
Published: May 2021

Granular substrates ranging from silt to gravel cover much of the Earth's land area, providing an important habitat for fossorial animals. Many of these animals use their heads to penetrate the substrate. Although there is considerable variation in head shape, how head shape affects fossorial locomotor performance in different granular substrates is poorly understood. Here, head shape variation for 152 species of fossorial lizards was quantified for head diameter, slope and pointiness of the snout. The force needed to penetrate different substrates was measured using 28 physical models spanning this evolved variation. Ten substrates were considered, ranging in particle size from 0.025 to 4 mm in diameter and consisting of spherical or angular particles. Head shape evolved in a weakly correlated manner, with snouts that were gently sloped being blunter. There were also significant clade differences in head shape among fossorial lizards. Experiments with physical models showed that as head diameter increased, absolute penetration force increased but force normalized by cross-sectional area decreased. Penetration force decreased for snouts that tapered more gradually and were pointier. Larger and angular particles required higher penetration forces, although intermediate size spherical particles, consistent with coarse sand, required the lowest force. Particle size and head diameter effect were largest, indicating that fossorial burrowers should evolve narrow heads and bodies, and select relatively fine particles. However, variation in evolved head shapes and recorded penetration forces suggests that kinematics of fossorial movement are likely an important factor in explaining evolved diversity.
Description and comparison of physical activity from self-reports and accelerometry among primary school children in Kilimanjaro, Tanzania: a pilot study
Authors: Mosha Mary Vincent , Kasagama Elizabeth , Ayieko Philip , Todd Jim , Msuya Sia E. , Grosskurth Heiner , Filteau Suzanne
Published: May 2021

Background: Self-reports are commonly used to assess physical activity in children. Existing self-reports for physical activity have not been validated for primary school children in Tanzania. To understand if primary school children can accurately report their physical activity, we examined the validity of self-reported physical activity against accelerometer measured physical activity.

Methods: A community-based cross-sectional study was conducted from May to July 2018. We conveniently selected four primary schools in Moshi municipal and Moshi rural districts in Kilimanjaro, Tanzania. From these districts, 51 children aged 9 – 11 years were randomly selected. A self-reported questionnaire was used to collect physical activity-related variables. Children wore accelerometers for seven consecutive days to capture physical activity movements. Spearman’s rank test and Bland Altman plots were used for assessing validity and agreement between self-reports and accelerometer moderate to vigorous physical activity (MVPA).

Results: The study participants' mean age was 10 (SD=0.8) years, and 32 (63%) were girls. A significant positive correlation was found between self-reports and accelerometer MVPA (rho=0.36, p=0.009). The mean total of weekday minutes in MVPA from accelerometers was higher than from self-reports, 408 (SD = 66) versus 261 (SD = 179).

Conclusions: This study found a significant positive correlation between self-reports and accelerometers. Self-reports are prone to errors due to recall bias, which interferes with their validity. More research is needed to develop better self-reported measures with specific activities that children can easily remember. Also, researchers should carefully consider the inherent limitations in the validity of self-reports.
Effectiveness of turmeric-enriched pellets to improve the immunity of Clarias batrachus toward motile Aeromonas septicemia disease
Authors: Riauwaty Morina , Siregar Yusni I. , Mulyani Isma
Published: May 2021

Background: Turmeric is known as a natural remedy to improve the immunity of organisms. This study aims to understand the effectiveness of turmeric-enriched pellets to improve the immunity of Clarias batrachus to Aeromonas hydrophila.

Methods: The study was conducted from May to August 2020. C. batrachus fingerlings, 7-8 cm total length (TL) and 4-5 g (BW) at baseline, were kept in 30 L aquaria (10 fishes/aquarium; three replicated/treatment). Commercial pellets were mixed with turmeric powder. There were five treatment groups: P0 (control, no turmeric); P1 (0.5 g turmeric per Kg of pellets); P2 (0.7 g/Kg); P3 (0.9 g/Kg); Pp (positive control). Thirty days after being feed with turmeric-enriched pellets, all groups of fish were infected with 0.1 ml (108) of A. hydrophila suspension, intramuscularly. The P0 group did not receive injection, while Pp group were not fed with turmeric-enriched pellets but were infected with the bacteria. Fourteen days after infection, clinical signs and hematology of the fish were studied.

Results: Pp fish showed heavy clinical signs of A. hydrophila, such as loss of balance, pigmentation, hemorrhages and ulcers. P0 fish did not show any symptoms, while the treated fish reveled some clinical signs of A. hydrophila to a lesser extent than Pp, indicating that the fish is able to face the A. hydrophila attack. Hematology for Pp fish revealed high white blood cells, indicating that the fish were infected. The blood condition of the P0 fish, as well as those of the turmeric-treated fish were normal. In general, the P3 fish showed the least clinical signs of A. hydrophila and normal blood condition, indicating that P3 treatment is best.

Conclusion: The best turmeric dosage to improve the immunity of C. batrachus toward A. hydrophila infection is 0.9 g/Kg pellets.
Identifying potential drug targets and candidate drugs for COVID-19: biological networks and structural modeling approaches
Authors: Selvaraj Gurudeeban , Kaliamurthi Satyavani , Peslherbe Gilles H. , Wei Dong-Qing
Published: May 2021

Background:Coronavirus (CoV) is an emerging human pathogen causing severe acute respiratory syndrome (SARS) around the world. Earlier identification of biomarkers for SARS can facilitate detection and reduce the mortality rate of the disease. Thus, by integrated network analysis and structural modeling approach, we aimed to explore the potential drug targets and the candidate drugs for coronavirus medicated SARS.

Methods:Differentially expression (DE) analysis of CoV infected host genes (HGs) expression profiles was conducted by using the Limma. Highly integrated DE-CoV-HGs were selected to construct the protein-protein interaction (PPI) network. 

Results:Using the Walktrap algorithm highly interconnected modules include module 1 (202 nodes); module 2 (126 nodes) and module 3 (121 nodes) modules were retrieved from the PPI network. MYC, HDAC9, NCOA3, CEBPB, VEGFA, BCL3, SMAD3, SMURF1, KLHL12, CBL, ERBB4, and CRKL were identified as potential drug targets (PDTs), which are highly expressed in the human respiratory system after CoV infection. Functional terms growth factor receptor binding, c-type lectin receptor signaling, interleukin-1 mediated signaling, TAP dependent antigen processing and presentation of peptide antigen via MHC class I, stimulatory T cell receptor signaling, and innate immune response signaling pathways, signal transduction and cytokine immune signaling pathways were enriched in the modules. Protein-protein docking results demonstrated the strong binding affinity (-314.57 kcal/mol) of the ERBB4-3cLpro complex which was selected as a drug target. In addition, molecular dynamics simulations indicated the structural stability and flexibility of the ERBB4-3cLpro complex. Further, Wortmannin was proposed as a candidate drug to ERBB4 to control SARS-CoV-2 pathogenesis through inhibit receptor tyrosine kinase-dependent macropinocytosis, MAPK signaling, and NF-kb singling pathways that regulate host cell entry, replication, and modulation of the host immune system.

Conclusion:We conclude that CoV drug target “ERBB4” and candidate drug “Wortmannin” provide insights on the possible personalized therapeutics for emerging COVID-19.
Correlation between anti-hypertensive drugs and disease progression among moderate, severe, and critically ill COVID-19 patients in the second referral hospital in Surbaya: A retrospective cohort study
Authors: Suryantoro Satriyo Dwi , Thaha Mochammad , Hayati Mutiara Rizky , Yusuf Mochammad , Pikir Budi Susetyo , Susilo Hendri
Published: May 2021

Background: Hypertension, as the comorbidity accompanying COVID-19, is related to angiotensin-converting enzyme 2 receptor (ACE-2R) and endothelial dysregulation which have an important role in blood pressure regulation. Other anti-hypertensive agents are believed to trigger the hyperinflammation process. We aimed to figure out the association between the use of anti-hypertensive drugs and the disease progression of COVID-19 patients.  

Methods: This study is an observational cohort study among COVID-19 adult patients from moderate to critically ill admitted to Universitas Airlangga Hospital (UAH) Surabaya with history of hypertension and receiving anti-hypertensive drugs.  

Results: Patients receiving beta blockers only had a longer length of stay than angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ACEI/ARB) or calcium channel blockers alone (17, 13.36, and 13.73 respectively), had the higher rate of intensive care unit (ICU) admission than ACEi/ARB (p 0.04), and had the highest mortality rate (54.55%). There were no significant differences in length of stay, ICU admission, mortality rate, and days of death among the single, double, and triple anti-hypertensive groups. The mortality rate in groups taking ACEi/ARB was lower than other combination.  

Conclusions: Hypertension can increase the severity of COVID-19. The use of ACEI/ARBs in ACE-2 receptor regulation which is thought to aggravate the condition of COVID-19 patients has not yet been proven. This is consistent with findings in other anti-hypertensive groups.
Spatial Capacity Planning
Authors: Besbes Omar , Castro Francisco , Lobel Ilan
Published: May 2021

We study the relationship between capacity and performance for a service firm with spatial operations, in the sense that requests arrive with origin-destination pairs. An example of such a system is a ride-hailing platform in which each customer arrives in the system with the need to travel from an origin to a destination. We propose a parsimonious representation of a spatial multiserver system through a state-dependent queueing model that captures spatial frictions as well as spatial economies of scale through the service rate. In a classical [Formula: see text] queueing model, the square root safety (SRS) staffing rule is known to balance server utilization and customer wait times. By contrast, we find that the SRS rule does not lead to such a balance in spatial systems. In a spatial environment, pick-up times increase the load in the system; furthermore, they are an endogenous source of extra workload that leads the system to only operate efficiently if there is sufficient imbalance between supply and demand. In heavy traffic, we derive the mapping from load to operating regimes and establish implications on various metrics of interest. In particular, to obtain a balance of utilization and wait times, the service firm should use a higher safety factor, proportional to the offered load to the power of [Formula: see text]. We also discuss implications of these results for general systems.
Diagnosis and staging of multiple myeloma using serum-based laser-induced breakdown spectroscopy combined with machine learning methods
Authors: Chen Xue , Zhang Yao , Li Xiaohui , Yang Ziheng , Liu Aichun , Yu Xin
Published: May 2021

Diagnosis and staging of multiple myeloma (MM) have been achieved using serum-based laser-induced breakdown spectroscopy (LIBS) in combination with machine learning methods. 130 cases of serum samples collected from registered MM patients in different progressive stages and healthy controls were deposited onto standard quantitative filter papers and ablated with a Q-switched Nd:YAG laser. Emissions of Ca, Na, K, Mg, C, H, O, N and CN were selected for malignancy diagnosis and staging. Multivariate statistics and machine learning methods, including principal component analysis (PCA), k-nearest neighbor (kNN), support vector machine (SVM) and artificial neural network (ANN) classifiers, were used to build the discrimination models. The performances of the classifiers were optimized via 10-fold cross-validation and evaluated in terms of accuracy, sensitivity, specificity, and area under the receiver operating characteristic curves (AUC). The kNN, SVM and ANN classifiers achieved comparable discrimination performances with accuracies of over 90% for both diagnosis and staging of MM. For diagnosis of MM, the classifiers achieved performances with AUC of ∼0.970, sensitivity of ∼0.930 and specificity of ∼0.910; for staging of MM, the corresponding values were AUC of ∼0.970, sensitivity of ∼0.910 and specificity of ∼0.930. These results show that the serum-based LIBS in combination with machine learning methods can serve as a fast, less invasive, cost-effective, and robust technique for diagnosis and staging of human malignancies.