bluuebunny/crossref_metadata_2025 huggingface dataset:
Magnetic resonance imaging characteristics in patients with spondyloarthritis and clinical diagnosis of heel enthesitis: post hoc analysis from the phase 3 ACHILLES trial
Authors: Baraliakos X. , Sewerin P. , de Miguel E. , Pournara E. , Kleinmond C. , Shekhawat A. , Jentzsch C. , Wiedon A. , Behrens F. ,   on behalf of the ACHILLES study group
Published: May 2022

Objective

To investigate the imaging characteristics and clinically assess heel enthesitis in spondyloarthritis (SpA) by applying in a post hoc analysis the Heel Enthesitis Magnetic Resonance Imaging Scoring system (HEMRIS) in blinded and centrally-read MRI data from the ACHILLES trial (NCT02771210).

Methods

ACHILLES included patients (≥18 years) with active psoriatic arthritis or axial SpA with clinical and MRI-positive heel enthesitis refractory to standard treatment. Patients were randomized to receive subcutaneous secukinumab 150/300 mg or placebo. At week 24, patients on placebo were switched to secukinumab treatment. MRI-positive heel enthesitis was confirmed in all patients by local investigators. MRIs were performed at 3 timepoints: screening and weeks 24 and 52. In the present analysis, all MRIs were re-evaluated by 2 blinded central readers in a consensus read fashion for a priori defined MRI parameters based on HEMRIS.

Results

At screening, 171/204 (83.8%) of patients presented with entheseal inflammation and/or structural damage, considering both the Achilles tendon and plantar fascia. Pathologies were more evident in the Achilles tendon area compared to the plantar aponeurosis. The most frequent pathologies were intra-tendon hypersignal and retrocalcaneal bursitis. The mean total entheseal inflammation score at screening in the Achilles tendon area was 2.99 (N=204) and the mean change (standard deviation [SD]) from screening to weeks 24 and 52 was − 0.91 (1.99) and − 0.83 (2.12) in the secukinumab group vs − 0.48 (1.86) and − 0.80 (1.98) in the placebo-secukinumab group, respectively. The mean total structural damage score at screening was 1.36 (N=204) and the mean change (SD) from screening to weeks 24 and 52 was 0.00 (0.65) and − 0.06 (0.56) in the secukinumab group vs 0.08 (0.48) and 0.04 (0.75) in the placebo-secukinumab group, respectively.

Conclusions

Based on the newly developed HEMRIS, entheseal inflammation and/or structural damage was confirmed in 83.3% of ACHILLES patients. Pathologies were more evident in the Achilles tendon area compared to plantar fascia, with the inflammatory parameters being more responsive with secukinumab treatment compared to placebo. The present analysis, with detailed information on individual MRI parameters, contributes to the scientific debate on heel enthesitis.

Trial registration

ClinicalTrials.gov NCT02771210.
Mesenchymal stromal cell-derived extracellular vesicles: novel approach in hematopoietic stem cell transplantation
Authors: Sarvar Davod Pashoutan , Effatpanah Hosein , Akbarzadehlaleh Parvin , Shamsasenjan Karim
Published: May 2022

Bone marrow mesenchymal stromal cells (MSCs) play a crucial role in the regulation of hematopoiesis. These cells affect the process through direct cell–cell contact, as well as releasing various trophic factors and extracellular vehicles (EVs) into the bone marrow microenvironment. MSC-derived EVs (MSC-EVs) are prominent intercellular communication tolls enriched with broad-spectrum bioactive factors such as proteins, cytokines, lipids, miRNAs, and siRNAs. They mimic some effects of MSCs by direct fusion with hematopoietic stem cells (HSC) membranes in the bone marrow (BM), thereby affecting HSC fate. MSC-EVs are attractive scope in cell-free therapy because of their unique capacity to repair BM tissue and regulate proliferation and differentiation of HSCs. These vesicles modulate the immune system responses and inhibit graft-versus-host disease following hematopoietic stem cell transplantation (HSCT). Recent studies have demonstrated that MSC-EVs play an influential role in the BM niches because of their unprecedented capacity to regulate HSC fate. Therefore, the existing paper intends to speculate upon the preconditioned MSC-EVs as a novel approach in HSCT.
Open sub-granting radio resources in overlay D2D-based V2V communications
Authors: Soleymani Dariush Moahammad , Gholami Mohammad Reza , Galdo Giovanni Del , Mueckenheim Jens , Mitschele-Thiel Andreas
Published: May 2022

Capacity, reliability, and latency are seen as key requirements of new emerging applications, namely vehicle-to-everything (V2X) and machine-type communication in future cellular networks. D2D communication is envisaged to be the enabler to accomplish the requirements for the applications as mentioned earlier. Due to the scarcity of radio resources, a hierarchical radio resource allocation, namely the sub-granting scheme, has been considered for the overlay D2D communication. In this paper, we investigate the assignment of underutilized radio resources from  D2D communication to device-to-infrastructure communication, which are moving in a dynamic environment. The sub-granting assignment problem is cast as a maximization problem of the uplink cell throughput. Firstly, we evaluate the sub-granting signaling overhead due to mobility in a centralized sub-granting resource algorithm, dedicated sub-granting radio resource (DSGRR), and then a distributed heuristics algorithm, open sub-granting radio resource (OSGRR), is proposed and compared with the DSGRR algorithm and no sub-granting case. Simulation results show improved cell throughput for the OSGRR compared with other algorithms. Besides, it is observed that the overhead incurred by the OSGRR is less than the DSGRR while the achieved cell throughput is yet close to the maximum achievable uplink cell throughput.
Video-based interviewing in medicine: a scoping review
Authors: Selvam Rajajee , Hu Richard , Musselman Reilly , Raiche Isabelle , McIsaac Daniel I. , Moloo Husein
Published: May 2022

Background

The Coronavirus 2019 pandemic necessitated a rapid uptake of video-based interviewing within the personnel selection process in healthcare. While video-based interviews have been evaluated previously, we identified a gap in the literature on the implementation of video-based interviews and how they compare to their face-to-face counterparts.

Methods

A scoping review was conducted to consolidate the available literature on the benefits and limitations of video-based interviews and to understand the perceived barriers associated with transitioning away from face-to-face interviews. A search strategy, developed in concert with an academic health sciences librarian, was run on Ovid MEDLINE, Embase, PsycInfo, and Cochrane Central. The search was performed on March 31, 2020, and updated on February 21, 2021. Studies that implemented and evaluated the impact of video-based interviewing in healthcare were included in our study. Review articles and editorials were excluded.

Results

Forty-three studies were included in our scoping review, of which 17 were conference abstracts and 26 were peer-reviewed manuscripts. The risk of bias was moderate or high in most studies, with only four studies having a low risk of bias. Both financial costs and opportunity costs associated with the selection process were reported to be improved with video-based interviewing, while no studies explored the impact on environmental costs. Technical limitations, which were not prevalent, were easily managed during the interview process. Overall, video-based interviews were well received by both applicants and interviewers, although most participants still reported a preference for face-to-face interviews.

Conclusions

While video-based interviewing has become necessary during the Coronavirus 2019 era, there are benefits from a financial, opportunistic, and environmental point of view that argue for its continued use even after the pandemic. Despite its successful implementation with minimal technical issues, a preference still remains for face-to-face interviews. Reasons for this preference are not clear from the available literature. Future studies on the role of nonverbal communication during the video-based interview process are important to better understand how video-based interviewing can be optimized.

Systematic review registration

This scoping review was registered with Open Science Framework.
The effect of active visual art therapy on health outcomes: protocol of a systematic review of randomised controlled trials
Authors: Joschko Ronja , Roll Stephanie , Willich Stefan N. , Berghöfer Anne
Published: May 2022

Background

Art therapy is a form of complementary therapy to treat a wide variety of health problems. Existing studies examining the effects of art therapy differ substantially regarding content and setting of the intervention, as well as their included populations, outcomes, and methodology. The aim of this review is to evaluate the overall effectiveness of active visual art therapy, used across different treatment indications and settings, on various patient outcomes.

Methods

We will include randomised controlled studies with an active art therapy intervention, defined as any form of creative expression involving a medium (such as paint etc.) to be actively applied or shaped by the patient in an artistic or expressive form, compared to any type of control. Any treatment indication and patient group will be included. A systematic literature search of the Cochrane Library, EMBASE (via Ovid), MEDLINE (via Ovid), CINAHL, ERIC, APA PsycArticles, APA PsycInfo, and PSYNDEX (all via EBSCOHost), ClinicalTrials.gov and the WHO’s International Clinical Trials Registry Platform (ICTRP) will be conducted. Psychological, cognitive, somatic and economic outcomes will be used. Based on the number, quality and outcome heterogeneity of the selected studies, a meta-analysis might be conducted, or the data synthesis will be performed narratively only. Heterogeneity will be assessed by calculating the p-value for the chi2 test and the I2 statistic. Subgroup analyses and meta-regressions are planned.

Discussion

This systematic review will provide a concise overview of current knowledge of the effectiveness of art therapy. Results have the potential to (1) inform existing treatment guidelines and clinical practice decisions, (2) provide insights to the therapy’s mechanism of change, and (3) generate hypothesis that can serve as a starting point for future randomised controlled studies.

Systematic review registration

PROSPERO ID CRD42021233272
What evidence exists on the effects of public policy interventions for achieving environmentally sustainable food consumption? A systematic map protocol
Authors: Macura Biljana , Ran Ylva , Persson U. Martin , Abu Hatab Assem , Jonell Malin , Lindahl Therese , Röös Elin
Published: May 2022

Background

The global food system is causing considerable environmental harm. A transition towards more sustainable consumption is needed. Targeted public policy interventions are crucial for stimulating such transition. While there is extensive research about the promotion of more environmentally sustainable food consumption, this knowledge is scattered across different sources. This systematic map aims to collate and describe the available evidence on public policy interventions such as laws, directives, taxes and information campaigns, for achieving sustainable food consumption patterns.

Methods

We will search bibliographic databases, specialist websites, Google Scholar and bibliographies of relevant reviews. Searches for academic literature will be performed in English, while searches for grey literature will be performed in English, Swedish, Danish and Norwegian. Screening, including consistency checking exercises, will be done at two levels: title and abstract, and full text. We will use machine learning algorithms to support screening at the title and abstract level. Coding and meta-data extraction will include bibliographic information, policy details and context, and measured environmental outcome(s). The evidence base will be summarised narratively using tables and graphs and presented as an online interactive searchable database and a website that will allow for visualisation, filtering and exploring systematic map findings, knowledge gaps and clusters.
Metabolic flux analysis of 3D spheroids reveals significant differences in glucose metabolism from matched 2D cultures of colorectal cancer and pancreatic ductal adenocarcinoma cell lines
Authors: Tidwell Tia R. , Røsland Gro V. , Tronstad Karl Johan , Søreide Kjetil , Hagland Hanne R.
Published: May 2022

Background

Most in vitro cancer cell experiments have been performed using 2D models. However, 3D spheroid cultures are increasingly favored for being more representative of in vivo tumor conditions. To overcome the translational challenges with 2D cell cultures, 3D systems better model more complex cell-to-cell contact and nutrient levels present in a tumor, improving our understanding of cancer complexity. Despite this need, there are few reports on how 3D cultures differ metabolically from 2D cultures.

Methods

Well-described cell lines from colorectal cancer (HCT116 and SW948) and pancreatic ductal adenocarcinoma (Panc-1 and MIA-Pa-Ca-2) were used to investigate metabolism in 3D spheroid models. The metabolic variation under normal glucose conditions were investigated comparing 2D and 3D cultures by metabolic flux analysis and expression of key metabolic proteins.

Results

We find significant differences in glucose metabolism of 3D cultures compared to 2D cultures, both related to glycolysis and oxidative phosphorylation. Spheroids have higher ATP-linked respiration in standard nutrient conditions and higher non-aerobic ATP production in the absence of supplemented glucose. In addition, ATP-linked respiration is significantly inversely correlated with OCR/ECAR (p= 0.0096). Mitochondrial transport protein, TOMM20, expression decreases in all spheroid models compared to 2D, and monocarboxylate transporter (MCT) expression increases in 3 of the 4 spheroid models.

Conclusions

In this study of CRC and PDAC cell lines, we demonstrate that glucose metabolism in 3D spheroids differs significantly from 2D cultures, both in terms of glycolytic and oxidative phosphorylation metrics. The metabolic phenotype shift from 2D to 3D culture in one cell line is greater than the phenotypic differences between each cell line and tumor source. The results herein emphasize the need to use 3D cell models for investigating nutrient utilization and metabolic flux for a better understanding of tumor metabolism and potential metabolic therapeutic targets.
A novel thermophilic chitinase directly mined from the marine metagenome using the deep learning tool Preoptem
Authors: Zhang Yan , Guan Feifei , Xu Guoshun , Liu Xiaoqing , Zhang Yuhong , Sun Jilu , Yao Bin , Huang Huoqing , Wu Ningfeng , Tian Jian
Published: May 2022

Chitin is abundant in nature and its degradation products are highly valuable for numerous applications. Thermophilic chitinases are increasingly appreciated for their capacity to biodegrade chitin at high temperatures and prolonged enzyme stability. Here, using deep learning approaches, we developed a prediction tool, Preoptem, to screen thermophilic proteins. A novel thermophilic chitinase, Chi304, was mined directly from the marine metagenome. Chi304 showed maximum activity at 85 ℃, its Tm reached 89.65 ± 0.22℃, and exhibited excellent thermal stability at 80 and 90 °C. Chi304 had both endo- and exo-chitinase activities, and the (GlcNAc)2 was the main hydrolysis product of chitin-related substrates. The product yields of colloidal chitin degradation reached 97% within 80 min, and 20% over 4 days of reaction with crude chitin powder. This study thus provides a method to mine the novel thermophilic chitinase for efficient chitin biodegradation.

Graphical Abstract
The mean platelet volume and atherosclerotic cardiovascular-risk factors in adults with obesity: a systematic review and meta-analysis of observational studies
Authors: Nkambule Bongani Brian , Mxinwa Vuyolwethu , Nyambuya Tawanda Maurice , Dludla Phiwayinkosi Vusi
Published: May 2022

Background

Obesity is a major risk factor for atherosclerotic cardiovascular disease (ASCVD) and is associated with altered platelet function. The mean platelet volume (MPV) is a rapid measure of platelet activation and a prognostic marker in patients with cardiovascular disease. However, no meta-analysis on the association between MPV and obesity has been conducted, and the value of monitoring the MPV in patients with obesity remains unclear.

Objective

To provide cumulative evidence on whether the mean platelet volume (MPV) is increased in individuals with obesity and to describe associations between the ASCVD-risk factors and the MPV in individuals with obesity.

Methods

This meta-analysis was prepared following the Meta-analysis Of Observational Studies (MOOSE) guidelines. We searched the PubMed and Embase database from inception until the 31st of March 2021. Studies were included when they reported the mean platelet volume in individuals with obesity and provided a suitable non-obese comparator group. The risk of bias was independently assessed by two reviewers using the Newcastle–Ottawa scale. The primary outcome of the meta-analysis was the MPV, while we considered the atherosclerotic risk profiles as a secondary outcome.

Results

We identified 178 citations through the PUBMED and 255 citations through EMBASE database search. In all, 13 studies met the inclusion criteria. Firstly, we report an increased mean platelet volume in individuals with obesity compared to non-obese individuals (MD 0.79; [95%CI: 0.42 to 1.16], I2 = 93.4%). Moreover, the reported increase in the MPV was inversely associated with the body mass index (Coefficient: -0.57, standard error (SE): 0.18, p < 0.001) and directly related to changes in triglyceride levels (Coefficient: 4.99, standard error (SE): 1.14, p < 0.001).

Conclusion

This meta-analysis and meta-regression showed an increased MPV in nondiabetic individuals living with obesity. Moreover, the MPV was associated with hypertriglyceridemia, an independent predictor of atherosclerotic cardiovascular disease. Overall, the findings suggest that MPV may be a valuable rapid marker for the monitoring and risk-stratification of individuals with obesity who may be at risk of developing cardiovascular disease.
Assuring Bangladesh’s future: non-communicable disease risk factors among the adolescents and the existing policy responses
Authors: Biswas Tuhin , Azzopardi Peter , Anwar Syeda Novera , de Vries Tim David , Encarnacion-Cruz Luis Manuel , Hasan Md. Mehedi , Huda M. Mamun , Pervin Sonia , Das Gupta Rajat , Mitra Dipak Kumar , Rawal Lal B. , Al Mamun Abdullah
Published: May 2022

Background

The aim of this study is to assess the current status of non-communicable disease (NCD) risk factors amongst adolescents in Bangladesh. We also critically reviewed the existing policy responses to NCD risk among adolescents in Bangladesh.

Methods

This study used a mixed method approach. To quantify the NCD risk burden, we used data from the Global School-based Student Health Survey conducted in Bangladesh. To understand policy response, we reviewed NCD-related policy documents introduced by the Government of Bangladesh between 1971 and 2018 using the WHO recommended NCD Action Plan 2013–2020as study framework. Information from the policy documents was extracted using a matrix, mapping each document against the six objectives of the WHO 2013–2020 Action Plan.

Results

Almost all adolescents in Bangladesh had at least one NCD risk factor, and there was a high prevalence of concurrent multiple NCD risk factors; 14% had one NCD risk factor while 22% had two, 29% had three, 34% had four or more NCD risk factors. Out of 38 policy documents, eight (21.1%) were related to research and/or surveys, eight (21.1%) were on established policies, and eleven (29%) were on legislation acts. Three policy documents (7.9%) were related to NCD guidelines and eight (21.1%) were strategic planning which were introduced by the government and non-government agencies/institutes in Bangladesh.

Conclusions

The findings emphasize the needs for strengthening NCD risk factors surveillance and introducing appropriate intervention strategies targeted to adolescents. Despite the Government of Bangladesh introducing several NCD-related policies and programs, the government also needs more focus on clear planning, implementation and monitoring and evaluation approaches to preventing NCD risk factors among the adolescents in Bangladesh.
The thin line that made the difference: a case report on a Bosniak IIF renal cystic mass treated with cyst decortication
Authors: Forookhi Ali , Bicchetti Marco , Lucciola Sara , Porreca Angelo , Busetto Gian Maria , Del Monte Maurizio
Published: May 2022

Background

Among all benign kidney lesions, renal cysts are the most common type. In the proposed update of 2019, the Bosniak classification of cystic renal masses is used to classify renal masses according to their likelihood of malignancy, both on computed tomography (CT) and on magnetic resonance imaging (MRI).

Case presentation

A middle-aged Caucasian male presented to our department with chronic right flank pain. Imaging studies revealed a right renal Bosniak IIF cyst, later complicated by traumatic haemorrhage. The patient consequently underwent cyst decortication for symptom relief. Biopsy results from samples taken during the laparoscopic operation revealed ISUP grade 1 cystic clear cell carcinoma.

Conclusion

The treatment of Bosniak IIF cysts has long been a matter of debate. As a result of scarcity of data on the probability of malignancy in MRI using the new classification, such cysts should be carefully scrutinised and staged before choosing a treatment option. Retroperitoneal seeding should always be considered in interventions involving an incomplete resection margin or cyst drainage.
A unified effective medium modeling framework for quantitative characterization of hydrate reservoirs
Authors: Pan Haojie , Li Hongbing , Wang Xiujuan , Cai Jianchao , Qian Jin , Howard James Jennings , Gao Qiang
Published: May 2022

Quantitative characterization of hydrate reservoirs is essential for evaluating hydrate resources and monitoring environmental hazards. Rock-physics models provide the theoretical basis for linking the hydrate saturation and distribution to the elastic properties. However, many of the existing models ignore the coupled effect of hydrate saturation and complex morphologies on the elastic behaviors and thereby fail to accurately describe hydrate reservoirs. To address these problems, the authors have proposed a unified effective medium modeling framework honoring multiple hydrate morphologies. In this framework, the manners in which the different types of hydrates interact with the sediment grains are characterized by different effective medium models. In addition to the hydrate saturation, the modeling results also reveal the effects of the cement factor, friction coefficient, incidence angle, lithology, and hydrate morphology on the elastic properties of the hydrate reservoirs. Then, five experimental data sets for synthetic methane and tetrahydrofuran hydrates formed under different conditions are used to validate the feasibility of the unified rock-physics modeling scheme. The good agreement between the theoretical predictions and laboratory data indicates that this method can effectively determine the hydrate occurrence mechanisms from the acoustic responses in different hydrate formation environments. On the basis of the constructed elastic rock-physics templates, multiple hydrate morphologies are determined with cluster analysis and then used for constraining the modeling scheme. Finally, the proposed modeling method is tested using sonic logs from Ignik Sikumi, North Slope of Alaska, and Hole U1518B, the northern Hikurangi margin, offshore New Zealand. The hydrate saturations estimated from the velocities are consistent with the interpretations based on resistivity and nuclear magnetic resonance logs, as well as chloride measurements, confirming the applicability and feasibility of our unified theoretical modeling framework.
Phantom subsurface targets in ground-penetrating radar data
Authors: Diamanti Nectaria , Annan A. Peter , Vargemezis Georgios
Published: May 2022

Ground-penetrating radar (GPR) has been a very effective tool for exploring the subsurface and the nondestructive testing of nonmetallic structures for the past 40–50 years. The traditional GPR data interpretation is built upon the innate bias that all signals emanate from within the ground and most GPR users are normally under the impression that energy mostly travels straight down leading to the perception that “targets” are beneath the measurement location. The response of features at the ground surface and above ground also is present in most data but not always consciously noted as contributing to the measurements. One class of responses from above-ground features is routinely called “airwaves” because they normally exhibit moveout velocities of air. Often, an above-ground source is not the first thing that comes to mind during data interpretation, unless the user is experienced. Even experienced users can occasionally be misled, as above-ground features are expected to reach the GPR receiver with the moveout velocity of air. Recent experience in some of our surveys has created concerns because the targets at or above the ground surface demonstrated ground wave moveout velocity, which eliminates one of the diagnostic tools. This paper explores this issue, identifies GPR signal paths, and suggests key factors to consider in field operations and data interpretation. To demonstrate the concepts described, we have used numerical modeling and field data sets.
Toward Incorporating Health-Related Quality of Life as Coprimary End Points in Clinical Trials: Time to Achieve Clinical Important Differences and QoL Profiles
Authors: Gebski Val , Obermair Andreas , Janda Monika
Published: May 2022

PURPOSE

Besides morbidity and mortality, quality of life (QoL) is a key outcome of cancer treatments. Trials on the basis of clinical outcomes have expectations that QoL outcomes can be either tolerated or improved. Simultaneously considering QoL and clinical outcomes is challenging with lack of suitable metrics allowing incorporation of QoL as coprimary end points in clinical trial design and utilization of hierarchical hypothesis testing.

METHOD

We propose combining time to achieving a minimal clinically important difference (MCID) and probabilities of a MCID occurring in each QoL domain to provide QoL metrics analogous to those used for clinical end points. For QoL domains of interest, these yield QoL profiles, time to MCID, and number needed to treat. Incorporation of QoL as coprimary end points in clinical trial designs through hierarchical hypothesis testing can easily be achieved. The noninferiority designed Laparoscopic Approach to Carcinoma of the Endometrium trial, evaluating laparoscopic versus open abdominal surgery for endometrial cancer with Functional Assessment of Cancer Therapy–General QoL domains, is used to illustrate the usefulness of these metrics.

RESULTS

This analysis revealed that laparoscopic surgery had a significant shorter time to MCID for physical and functional well-being QoL domains (physical mean: 1.5 months, 95% CI, 0.5 to 2.6; P = .002; and functional mean: 1.4 months; 95% CI, 0.4 to 2.4; P = .003) than abdominal surgery, but little difference between the two approaches for psychologic social and emotion well-being. Probability profile plots show a consistent > 2-fold higher chance of attaining a MCID for physical and functional well-being over time for laparoscopic compared with abdominal surgery.

CONCLUSION

This analysis reinforces the potential value of novel MCID metrics and their usefulness in raising the profile of QoL outcomes to complement clinical end points. The methods will allow health professionals to counsel patients about QoL outcomes and clinical outcomes simultaneously.
Prevalence and Phenotypic Effects of Copy Number Variants in Isolated Hypogonadotropic Hypogonadism
Authors: Stamou Maria I , Brand Harrison , Wang Mei , Wong Isaac , Lippincott Margaret F , Plummer Lacey , Crowley William F , Talkowski Michael , Seminara Stephanie , Balasubramanian Ravikumar
Published: May 2022

Context

The genetic architecture of isolated hypogonadotropic hypogonadism (IHH) has not been completely defined.

Objective

To determine the role of copy number variants (CNVs) in IHH pathogenicity and define their phenotypic spectrum.

Methods

Exome sequencing (ES) data in IHH probands (n = 1394) (Kallmann syndrome [IHH with anosmia; KS], n = 706; normosmic IHH [nIHH], n = 688) and family members (n = 1092) at the Reproductive Endocrine Unit and the Center for Genomic Medicine of Massachusetts General Hospital were analyzed for CNVs and single nucleotide variants (SNVs)/indels in 62 known IHH genes. IHH subjects without SNVs/indels in known genes were considered “unsolved.” Phenotypes associated with CNVs were evaluated through review of patient medical records. A total of 29 CNVs in 13 genes were detected (overall IHH cohort prevalence: ~2%). Almost all (28/29) CNVs occurred in unsolved IHH cases. While some genes (eg, ANOS1 and FGFR1) frequently harbor both CNVs and SNVs/indels, the mutational spectrum of others (eg, CHD7) was restricted to SNVs/indels. Syndromic phenotypes were seen in 83% and 63% of IHH subjects with multigenic and single gene CNVs, respectively.

Conclusion

CNVs in known genes contribute to ~2% of IHH pathogenesis. Predictably, multigenic contiguous CNVs resulted in syndromic phenotypes. Syndromic phenotypes resulting from single gene CNVs validate pleiotropy of some IHH genes. Genome sequencing approaches are now needed to identify novel genes and/or other elusive variants (eg, noncoding/complex structural variants) that may explain the remaining missing etiology of IHH.
Béroalde de Verville, médecin conteur, et la seconde vie de la Querelle de l’Abstinente (1612)
Authors: Winn Colette H.
Published: May 2022

La Querelle de l’abstinente, suite à la parution, en 1566, puis en 1597, du Huitiesme Paradoxe de Laurent Joubert, opposa dans un premier temps le médecin orléanais, Israël Harvet, au médecin poitevin, François Citoys, autour de la question de savoir combien de temps un être humain peut rester en vie sans boire ni manger. Le médecin tourangeau, Béroalde de Verville, s’était d’abord rangé du côté d’Harvet qui réfutait les arguments de Citoys en faveur de la thèse avancée par Joubert. En 1612, alors que la Querelle de l’Abstinente a pratiquement sombré dans l’oubli, le conteur Béroalde de Verville lui redonne une seconde vie. Dans Le Palais des Curieux (Object XVIII), il consacre à la question des abstinences extraordinaires trois brefs récits intitulés « D’une fille qui vivait sans manger », « De l’Epimenidium » et « D’un homme fort sobre ». Nous nous proposons de relire ces textes en nous interrogeant sur 1) les motivations qui ont pu conduire Béroalde de Verville à relancer un débat depuis longtemps classé ; 2) les choix auctoriaux – celui de traiter d’une question médicale sous la forme d’historiettes et celui d’insérer celles-ci dans un recueil de curiosités assemblé « pour le plaisir des Doctes et le bien de ceux qui desirent toujours savoir » ; et 3) la nouvelle dimension que prend alors l’ancienne querelle d’école.
Dining with the Hermaphrodites
Authors: Long Kathleen
Published: May 2022

The régime de santé, already by the end of the medieval era a well-developed genre that offered advice on diet and other health practices, found new life in the sixteenth century as the Galenic works on food and hygiene that informed it were translated into Latin and even into vernacular languages. The precepts of this genre entered into the literary culture of early modern France primarily through the avenue of satire, in which characters were defined by the food they ate and by other aspects of the Galenic regimen. Because of its association with treatises on the education of princes, the régime de santé took a political turn, something that is also echoed in satirical literature. One clear example of the politics of the régime de santé is the banquet scene of L’Isle des hermaphrodites (The Island of Hermaphrodites), published in 1605 and circulated widely in Paris. This novel seems at first glance to be a fairly straightforward satire of the excesses of the court of Henri III of France (r. 1574–1589). Yet the banquet scene evokes the flexibility of diet and of other aspects of the Galenic regimen in the profusion and variety of food presented. In linking the practices of the hermaphrodites to contemporary works on the régime de santé, this novel suggests another possibility: a world where the needs of an individual living in a particular environment are met with a diet and way of life appropriate to those needs. In presenting this alternative view, the novel raises the question whether such individualized care is merely self-indulgent or whether it is very much needed in the aftermath of the massive trauma of the Wars of Religion.
Teresa de Cartagena’s Illness and Disability as Embodied Knowledge
Authors: Kim Yonsoo
Published: May 2022

Physical illness may lead women to grow spiritually, reflect on their lives, and learn how to write about their unique experiences. A fifteenth-century Castilian writer, Teresa de Cartagena distinguishes herself for being a nun, a conversa, a member of a powerful Jewish family, and most of all a disabled (deaf) woman of letters. Her work Arboleda de los enfermos represents a hybrid paradigm in which literature, religion, and medicine interact with one another in medieval Europe. Teresa’s use of embodied metaphors to describe her experience of isolation and loneliness helps reorient readers’ understanding of the disability narrative. Suffering itself serves as an embodiment of consolation and as a medical and religious treatment that relieves her suffering. This article argues that to objectively examine her illness and disability, Teresa deploys intersectional knowledge to interpret her experience, and to empower herself and those who are suffering from the same condition, asserting that deafness, like any other physical impairment, is not a social or religious punishment but rather a “privileged” condition.
State Policies and Health Disparities between Transgender and Cisgender Adults: Considerations and Challenges Using Population-Based Survey Data
Authors: Gonzales Gilbert , Tran Nathaniel M. , Bennett Marcus A.
Published: May 2022

Context: The authors examined the association between state-level policy protections and self-rated health disparities between transgender and cisgender adults.

Methods: They used data on transgender (n = 4,982) and cisgender (n = 1,168,859) adults from the 2014–2019 Behavioral Risk Factor Surveillance System. The authors estimated state-specific health disparities between transgender and cisgender adults, and they used multivariable logistic regression models to compare adjusted odds ratios between transgender and cisgender adults by state-level policy environments.

Findings: Transgender adults were significantly more likely to report poor/fair health, frequent mental distress, and frequent poor physical health days compared to cisgender adults. Disparities between transgender and cisgender adults were found in states with strengthened protections and in states with limited protections. Compared to transgender adults in states with limited protections, transgender adults in states with strengthened protections were marginally less likely to report frequent mental distress.

Conclusions: Transgender adults in most states reported worse self-rated health than their cisgender peers. Much more research and robust data collection on gender identity are needed to study the associations between state policies and transgender health and to identify best practices for achieving health equity for transgender Americans.
A Life in “Parcels”
Authors: Neil Kelly
Published: May 2022

This article examines how instructors may engage students in literature courses by leveraging students’ affective responses through a digital commonplace book. Corresponding to representations of identity in Shakespeare's 1603 play Othello, the commonplace book allows students to curate texts and consider how such arrangements reflect and construct their self-narratives.
Pedagogies of the Mad
Authors: Tinkle Theresa
Published: May 2022

This article reports on an undergraduate course centered on autobiographies written by people who manage mental illnesses. Students learned about neurodiversity from multiple perspectives, examined social and medical models of mental illness, developed interpretive skills, and advanced their ability to write compellingly about both literature and their own experiences.
Functions of the FGF signalling pathway in cephalochordates provide insight into the evolution of the prechordal plate
Authors: Meister Lydvina , Escriva Hector , Bertrand Stéphanie
Published: May 2022

The fibroblast growth factor (FGF) signalling pathway plays various roles during vertebrate embryogenesis, from mesoderm formation to brain patterning. This diversity of functions relies on the fact that vertebrates possess the largest FGF gene complement among metazoans. In the cephalochordate amphioxus, which belongs to the chordate clade together with vertebrates and tunicates, we have previously shown that the main role of FGF during early development is the control of rostral somite formation. Inhibition of this signalling pathway induces the loss of these structures, resulting in an embryo without anterior segmented mesoderm, as in the vertebrate head. Here, by combining several approaches, we show that the anterior presumptive paraxial mesoderm cells acquire an anterior axial fate when FGF signal is inhibited and that they are later incorporated in the anterior notochord. Our analysis of notochord formation in wild type and in embryos in which FGF signalling is inhibited also reveals that amphioxus anterior notochord presents transient prechordal plate features. Altogether, our results give insight into how changes in FGF functions during chordate evolution might have participated to the emergence of the complex vertebrate head.
Aberrant uterine folding in mice disrupts implantation chamber formation and alignment of embryo-uterine axes
Authors: Madhavan Manoj K. , DeMayo Francesco J. , Lydon John P. , Joshi Niraj R. , Fazleabas Asgerally T. , Arora Ripla
Published: May 2022

The uterine luminal epithelium folds characteristically in mammals, including humans, horses and rodents. Improper uterine folding in horses results in pregnancy failure, but the precise function of folds remains unknown. Here, we uncover dynamic changes in the 3D uterine folding pattern during early pregnancy with the entire lumen forming pre-implantation transverse folds along the mesometrial-antimesometrial axis. Using a time course, we show that transverse folds are formed before embryo spacing, whereas implantation chambers form as the embryo begins attachment. Thus, folds and chambers are two distinct structures. Transverse folds resolve to form a flat implantation region, after which an embryo arrives at its center to attach and form the post-implantation chamber. Our data also suggest that the implantation chamber facilitates embryo rotation and its alignment along the uterine mesometrial-antimesometrial axis. Using WNT5A- and RBPJ-deficient mice that display aberrant folds, we show that embryos trapped in longitudinal folds display misalignment of the embryo-uterine axes, abnormal chamber formation and defective post-implantation morphogenesis. These mouse models with disrupted uterine folding provide an opportunity to understand uterine structure-based mechanisms that are crucial for implantation and pregnancy success.

This article has an associated ‘The people behind the papers’ interview.
Roles of the actin cytoskeleton in ciliogenesis
Authors: Hoffman Huxley K. , Prekeris Rytis
Published: May 2022

Primary cilia play a key role in the ability of cells to respond to extracellular stimuli, such as signaling molecules and environmental cues. These sensory organelles are crucial to the development of many organ systems, and defects in primary ciliogenesis lead to multisystemic genetic disorders, known as ciliopathies. Here, we review recent advances in the understanding of several key aspects of the regulation of ciliogenesis. Primary ciliogenesis is thought to take different pathways depending on cell type, and some recent studies shed new light on the cell-type-specific mechanisms regulating ciliogenesis at the apical surface in polarized epithelial cells, which are particularly relevant for many ciliopathies. Furthermore, recent findings have demonstrated the importance of actin cytoskeleton dynamics in positively and negatively regulating multiple stages of ciliogenesis, including the vesicular trafficking of ciliary components and the positioning and docking of the basal body. Finally, studies on the formation of motile cilia in multiciliated epithelial cells have revealed requirements for actin remodeling in this process too, as well as showing evidence of an additional alternative ciliogenesis pathway.
Glucose tolerance predicts survival in old zebra finches
Authors: Montoya Bibiana , Briga Michael , Jimeno Blanca , Verhulst Simon
Published: May 2022

The capacity to deal with external and internal challenges is thought to affect fitness, and the age-linked impairment of this capacity defines the ageing process. Using a recently developed intra-peritoneal glucose tolerance test (GTT), we tested for a link between the capacity to regulate glucose levels and survival in zebra finches. We also investigated for the effects of ambient factors, age, sex, and manipulated developmental and adult conditions (i.e. natal brood size and foraging cost, in a full factorial design) on glucose tolerance. Glucose tolerance was quantified using the incremental ‘area under the curve’ (AUC), with lower values indicating higher tolerance. Glucose tolerance predicted survival probability in old birds, above the median age, with individuals with higher glucose tolerance showing better survival than individuals with low or intermediate glucose tolerance. In young birds there was no association between glucose tolerance and survival. Experimentally induced adverse developmental conditions did not affect glucose tolerance, but low ambient temperature at sampling and hard foraging conditions during adulthood induced a fast return to baseline levels (i.e. high glucose tolerance). These findings can be interpreted as an efficient return to baseline glucose levels when energy requirements are high, with glucose presumably being used for energy metabolism or storage. Glucose tolerance was independent of sex. Our main finding that old birds with higher glucose tolerance had better survival supports the hypothesis that the capacity to efficiently cope with a physiological challenge predicts lifespan, at least in old birds.
Activation of p53 in anoxic freshwater crayfish, Faxonius virilis
Authors: Gupta Aakriti , Breedon Sarah A. , Storey Kenneth B.
Published: May 2022

Tumor suppressing transcription factor p53 regulates multiple pathways including DNA repair, cell survival, apoptosis and autophagy. Here, we studied the stress-induced activation of p53 in anoxic crayfish (Faxonius virilis). Relative levels of target proteins and mRNAs involved in the DNA damage response were measured in normoxic control and anoxic hepatopancreas and tail muscle. Phosphorylation levels of p53 were assessed using immunoblotting at sites known to be phosphorylated (serine 15 and 37) in response to DNA damage or reduced oxygen signaling. The capacity for DNA binding by phosphorylated p53 (p-p53) was also measured, followed by transcript analysis of a potentially pro-apoptotic downstream target, the etoposide induced (ei24) gene. Following this, both inhibitor (MDM2) and activator (p19-ARF) protein levels in response to low-oxygen stress were studied. The results showed an increase in p-p53 levels during anoxia in both hepatopancreas and tail muscle. Increased transcript levels of ei24 support the activation of p53 under anoxic stress. Cytoplasmic accumulation of Ser15 phosphorylated p53 was observed during anoxia when proteins from cytoplasmic and nuclear fractions were measured. Increased cytoplasmic concentration is known to initiate an apoptotic response, which can be assumed as a preparatory step to prevent autophagy. The results suggest that p53 might play a protective role in crayfish defense against low-oxygen stress. Understanding how anoxia-tolerant organisms are able to protect themselves against DNA damage could provide important clues towards survival under metabolic rate depression and preparation for recovery to minimize damage.
Analysis of the paddy fields to support community and tourism activities in Ciemas District, Indonesia
Authors: Syiddatul Akliyah Lely , Hindersah Hilwati , Hanif Fikri Muhammad
Published: May 2022

Ciletuh Geopark Tourism Area (UNESCO Global Geopark Ciletuh Palabuhanratu) is now one of the main tourist attractions in the Sukabumi Regency, West Java province of Indonesia. The geopark area is in the Ciemas District. Based on the Regional Spatial Planning of the Sukabumi Regency, the Ciemas District is designated as the center of the agricultural sector activities for paddy rice plants in the Sukabumi District. Through the development of tourism activities, Ciletuh Palabuhanratu Geopark will undoubtedly threaten the rice farming sector in the area. In the disruption era, as technology changes, information and knowledge become more accessible. The development of these tourism activities will grow faster in Ciemas District, causing many changes, especially in physical space and regional economics. One change would be in the rice fields in this area, which has been transformed into built-in land in villas, inns, and homestays. If this is allowed, then the function of the sustainability of agricultural activities in the Ciemas District will be threatened. For this reason, control efforts are needed so that paddy fields that must be maintained do not change function quickly. This study analyzes the land use and land cover for paddy fields in Ciemas District. The method of this study is the quantitative method. The analytical methods include population projection, ArcGIS analysis, and Land Potential Index. The findings contribute to supporting the development of tourism while maintaining food security. The results indicate that there are protected areas from being prioritized, which are not prioritized for paddy fields, can be used for the development of tourism activities. Thus, this can be used as a source for the government to make policies for fulfilling food requirements and developing tourism activities in the region.