bluuebunny/crossref_metadata_2025 huggingface dataset:
Association between temperature exposure and cognition: a cross-sectional analysis of 20,687 aging adults in the United States
Authors: Khan Anam M. , Finlay Jessica M. , Clarke Philippa , Sol Ketlyne , Melendez Robert , Judd Suzanne , Gronlund Carina J.
Published: July 2021

Background

Older adults are particularly vulnerable to the adverse health effects of extreme temperature-related events. A growing body of literature highlights the importance of the natural environment, including air pollution and sunlight, on cognitive health. However, the relationship between exposure to outdoor temperatures and cognitive functioning, and whether there exists any differences across climate region, remains largely unexplored. We address this gap by examining the temperature-cognition association, and whether there exists any variation across climate regions in a national cohort of aging adults.

Methods

In this cross-sectional study, we obtained data on temperature exposure based on geocoded residential location of participants in the REasons for Geographic And Racial Differences in Stroke (REGARDS) study. For each participant, this information was linked to their cognitive scores from Word List Learning and Recall tests to assess cognitive functioning. We used distributed lag non-linear models (dlnm) to model temperature effects over 2 days. Multivariable linear regression was used to compute temperature-cognitive functioning associations, adjusted for important covariates. Region-specific (“Dry”, “Mediterranean/oceanic”, “Tropical” and “Continental”) associations were examined by including an interaction term between climate region and temperature.

Results

Amongst 20,687 individuals (mean age = 67.8; standard deviation = 9.2), exposure to region-specific extreme cold temperatures in the “dry” region (e.g., Arizona) over 2 days was associated with lower cognitive scores (Mean Difference [MD]: -0.76, 95% Confidence Interval [CI]: − 1.45, − 0.07). Associations remained significant for cumulative effects of temperature over 2 days. Extremely cold exposure in the “Mediterranean/oceanic” region (e.g., California) over 2 days was also associated with significantly lower cognitive performance (MD: -0.25, 95% CI: − 0.47, − 0.04). No significant associations were observed for exposure to hot temperatures. Cognitive performance was slightly higher in late summer and fall compared to early summer.

Conclusion

We noted adverse cognitive associations with cold temperatures in traditionally warmer regions of the country and improved cognition in summer and early fall seasons. While we did not observe very large significant associations, this study deepens understanding of the impact of climate change on the cognitive health of aging adults and can inform clinical care and public health preparedness plans.
Using a self-directed workbook to support advance care planning with long term care home residents
Authors: Sussman Tamara , Kaasalainen Sharon , Lawrence Jack , Hunter Paulette V. , Bourgeois-Guerin Valerie , Howard Michelle
Published: July 2021

Background

While advance care planning (ACP) has been shown to improve the quality of end-of-life (EOL) communication and palliative care, it is rarely practiced in long term care (LTC) homes, where staff time to support the process is limited. This study examines the potential of a publicly available self-directed ACP workbook distributed to LTC residents to encourage ACP reflection and communication.

Methods

Recruitment took place across three LTC homes, between June 2018 and July 2019. To be eligible, residents had to have medical stability, cognitive capacity, and English literacy. The study employed a mixed methods concurrent design using the combination of ranked (quantitative) and open (qualitative) workbook responses to examine documented care preferences and ACP reflections and communications.

Results

58 residents initially agreed to participate in the study of which 44 completed self-directed ACP workbooks. Our combined quantitative and qualitative results suggested that the workbooks supported the elicitation of a range of resident care preferences of relevance for EOL care planning and decision making. For example, ranked data highlighted that most residents want to remain involved in decisions pertaining to their care (70%), even though less than half expect their wishes to be applied without discretion (48%). Ranked data further revealed many residents value quality of life over quantity of life (55%) but a sizable minority are concerned they will not receive enough care at EOL (20%). Open comments affirmed and expanded on ranked data by capturing care preferences not explored in the ranked data such as preferences around spiritual care and post mortem planning. Analysis of all open comments also suggested that while the workbook elicited many reflections that could be readily communicated to family/friends or staff, evidence that conversations had occurred was less evident in recorded workbook responses.

Conclusions

ACP workbooks may be useful for supporting the elicitation of resident care preferences and concerns in LTC. Developing follow up protocols wherein residents are supported in communicating their workbook responses to families/friends and staff may be a critical next step in improving ACP engagement in LTC. Such protocols would require staff training and an organizational culture that empowers staff at all levels to engage in follow up conversations with residents.
Medical errors during training: how do residents cope?: a descriptive study
Authors: Fatima Saba , Soria Stefania , Esteban- Cruciani Nora
Published: July 2021

Background

Physicians’ self-perceived medical errors lead to substantial emotional distress, which has been termed the “second victim phenomenon.” Medical errors during residency are associated with increased burnout and depression. It is important to know how residents cope with self-perceived medical errors and how they gain personal and emotional support in order to develop effective interventions.

Objective

To assess the impact of self-perceived medical errors on residents’ well-being, the range of coping strategies during training, and the extent of personal and institutional support.

Methods

An online cross-sectional survey was administered via email in October 2018 to 286 residents across all specialties in a 548-bed single urban academic medical center. The survey covered three domains focusing on residents’ most serious self-perceived medical error: (1) emotional response, (2) coping strategies using the BRIEF COPE Inventory, and (3) personal and institutional support.

Results

109/286 residents from various specialties responded. Internal Medicine, Pediatrics and Emergency Medicine constituting 80 % of respondents. Self-perceived medical errors during residency were widespread (95 %). One in five medical errors was classified as moderate to severe. Most residents acknowledged a sense of guilt, remorse and/or inadequacy. Use of maladaptive coping strategies was high. Open-ended responses pointed to fear of retaliation, judgement, shame and retribution. Most residents disclosed their error to a senior resident but did not discuss it with the patient’s family. Only 32 % of residents participated in a debriefing session.

Conclusions

Most residents were directly involved in medical errors, which affected their emotional well-being. The use of maladaptive coping strategies was high. Residents’ fear of consequences prevented disclosure and discussion of self-perceived medical errors. This information is relevant to implement targeted interventions.
Engaging young people in the design of a sexual reproductive health intervention: Lessons learnt from the Yathu Yathu (“For us, by us”) formative study in Zambia
Authors: Simuyaba Melvin , Hensen Bernadette , Phiri Mwelwa , Mwansa Chisanga , Mwenge Lawrence , Kabumbu Mutale , Belemu Steve , Shanaube Kwame , Schaap Ab , Floyd Sian , Fidler Sarah , Hayes Richard , Ayles Helen , Simwinga Musonda
Published: July 2021

Background

Meeting the sexual and reproductive health (SRH) needs of adolescents and young people (AYP) requires their meaningful engagement in intervention design. We describe an iterative process of engaging AYP to finalise the design of a community-based, peer-led and incentivised SRH intervention for AYP aged 15–24 in Lusaka and the lessons learnt.

Methods

Between November 2018 and March 2019, 18 focus group discussions, eight in-depth interviews and six observations were conducted to assess AYP’s knowledge of HIV/SRH services, factors influencing AYP’s sexual behaviour and elicit views on core elements of a proposed intervention, including: community-based spaces (hubs) for service delivery, type of service providers and incentivising service use through prevention points cards (PPC; “loyalty” cards to gain points for accessing services and redeem these for rewards). A total of 230 AYP (15 participated twice in different research activities) and 21 adults (only participated in the community mapping discussions) participated in the research. Participants were purposively selected based on age, sex, where they lived and their roles in the study communities. Data were analysed thematically.

Results

Alcohol and drug abuse, peer pressure, poverty, unemployment and limited recreation facilities influenced AYP’s sexual behaviours. Adolescent boys and young men lacked knowledge of contraceptive services and all AYP of pre and post exposure prophylaxis for HIV prevention. AYP stated a preference for accessing services at “hubs” located in the community rather than the health facility. AYP considered the age, sex and training of the providers when choosing whom they were comfortable accessing services from. PPCs were acceptable among AYP despite the loyalty card concept being new to them. AYP suggested financial and school support, electronic devices, clothing and food supplies as rewards.

Conclusions

Engaging AYP in the design of an SRH intervention was feasible, informative and considered responsive to their needs. Although AYP’s suggestions were diverse, the iterative process of AYP engagement facilitated the design of an intervention that is informed by AYP and implementable.

Trial registration

This formative study informed the design of this trial: ClinicalTrials.gov, NCT04060420. Registered 19 August, 2019.
The scope of carer effects and their inclusion in decision-making: a UK-based Delphi study
Authors: Al-Janabi Hareth , Efstathiou Nikolaos , McLoughlin Carol , Calvert Melanie , Oyebode Jan
Published: July 2021

Background and objective

Health and social care may affect unpaid (family) carers’ health and wellbeing in addition to patients’ lives. It is recommended that such impacts (carer effects) are considered in decision-making. However, the scope of carer effects and range of decisions where carer effects should be considered is uncertain. This study aimed to identify: (i) how different categories of healthcare and social care were perceived to impact on unpaid carers; and (ii) whether there was consensus about when carer effects should be formally considered in decision-making contexts.

Methods

A two round, online Delphi study was conducted with 65 UK-based participants (unpaid carers, care professionals, and researchers) with expertise in dementia, mental health, and stroke. Participants considered two broad forms of ‘interventions’ (patient treatment and replacement care) and two broad forms of ‘organisational change’ (staffing and changes in timing/location of care). Participants assessed the likely impacts of these on unpaid carers and whether impacts should be considered in decision-making.

Results

Participants predicted interventions and organisational changes would impact on multiple domains of unpaid carers’ lives, with ‘emotional health’ the most likely outcome to be affected. Patient treatment and replacement care services (‘interventions’) were associated with positive impacts across all domains. Conversely, timing/location changes and staffing changes (‘organisational changes’) were perceived to have mixed and negative impacts. There was widespread support (80–81 %) for considering carer effects in research studies, funding decisions, and patient decision-making.

Conclusions

This study highlights a perception that carer effects are widespread and important to consider in economic evaluation and decision-making. It highlights the particular need to measure and value effects on carers’ emotional health and the need to use a societal perspective to avoid cost shifting to unpaid carers when introducing interventions and making organisational changes.
Profiling non-coding RNA levels with clinical classifiers in pediatric Crohn’s disease
Authors: Pelia Ranjit , Venkateswaran Suresh , Matthews Jason D. , Haberman Yael , Cutler David J. , Hyams Jeffrey S. , Denson Lee A. , Kugathasan Subra
Published: July 2021

Background

Crohn’s disease (CD) is a heritable chronic inflammatory disorder. Non-coding RNAs (ncRNAs) play an important role in epigenetic regulation by affecting gene expression, but can also directly affect protein function, thus having a substantial impact on biological processes. We investigated whether non-coding RNAs (ncRNA) at diagnosis are dysregulated during CD at different CD locations and future disease behaviors to determine if ncRNA signatures can serve as an index to outcomes.

Methods

Using subjects belonging to the RISK cohort, we analyzed ncRNA from the ileal biopsies of 345 CD and 71 non-IBD controls, and ncRNA from rectal biopsies of 329 CD and 61 non-IBD controls. Sequence alignment was done (STAR package) using Human Genome version 38 (hg38) as reference panel. The differential expression (DE) analysis was performed with EdgeR package and DE ncRNAs were identified with a threshold of fold change (FC) > 2 and FDR < 0.05 after multiple test corrections.

Results

In total, we identified 130 CD specific DE ncRNAs (89 in ileum and 41 in rectum) when compared to non-IBD controls. Similarly, 35 DE ncRNAs were identified between B1 and B2 in ileum, whereas no differences among CD disease behaviors were noticed in rectum. We also found inflammation specific ncRNAs between inflamed and non-inflamed groups in ileal biopsies. Overall, we observed that expression of mir1244-2, mir1244-3, mir1244-4, and RN7SL2 were increased during CD, regardless of disease behavior, location, or inflammatory status. Lastly, we tested ncRNA expression at baseline as potential tool to predict the disease status, disease behaviors and disease inflammation at 3-year follow up.

Conclusions

We have identified ncRNAs that are specific to disease location, disease behavior, and disease inflammation in CD. Both ileal and rectal specific ncRNA are changing over the course of CD, specifically during the disease progression in the intestinal mucosa. Collectively, our findings show changes in ncRNA during CD and may have a clinical utility in early identification and characterization of disease progression.
Circular RNA circIKBKB promotes breast cancer bone metastasis through sustaining NF-κB/bone remodeling factors signaling
Authors: Xu Yingru , Zhang Shuxia , Liao Xinyi , Li Man , Chen Suwen , Li Xincheng , Wu Xingui , Yang Meisongzhu , Tang Miaoling , Hu Yameng , Li Ziwen , Yu Ruyuan , Huang Mudan , Song Libing , Li Jun
Published: July 2021

Background

Breast cancer (BC) has a marked tendency to spread to the bone, resulting in significant skeletal complications and mortality. Recently, circular RNAs (circRNAs) have been reported to contribute to cancer initiation and progression. However, the function and mechanism of circRNAs in BC bone metastasis (BC-BM) remain largely unknown.

Methods

Bone-metastatic circRNAs were screened using circRNAs deep sequencing and validated using in situ hybridization in BC tissues with or without bone metastasis. The role of circIKBKB in inducing bone pre-metastatic niche formation and bone metastasis was determined using osteoclastogenesis, immunofluorescence and bone resorption pit assays. The mechanism underlying circIKBKB-mediated activation of NF-κB/bone remodeling factors signaling and EIF4A3-induced circIKBKB were investigated using RNA pull-down, luciferase reporter, chromatin isolation by RNA purification and enzyme-linked immunosorbent assays.

Results

We identified that a novel circRNA, circIKBKB, was upregulated significantly in bone-metastatic BC tissues. Overexpressing circIKBKB enhanced the capability of BC cells to induce formation of bone pre-metastatic niche dramatically by promoting osteoclastogenesis in vivo and in vitro. Mechanically, circIKBKB activated NF-κB pathway via promoting IKKβ-mediated IκBα phosphorylation, inhibiting IκBα feedback loop and facilitating NF-κB to the promoters of multiple bone remodeling factors. Moreover, EIF4A3, acted acting as a pre-mRNA splicing factor, promoted cyclization of circIKBKB by directly binding to the circIKBKB flanking region. Importantly, treatment with inhibitor eIF4A3-IN-2 reduced circIKBKB expression and inhibited breast cancer bone metastasis effectively.

Conclusion

We revealed a plausible mechanism for circIKBKB-mediated NF-κB hyperactivation in bone-metastatic BC, which might represent a potential strategy to treat breast cancer bone metastasis.
GenoVault: a cloud based genomics repository
Authors: Jain Sankalp , Saxena Amit , Hesarur Suprit , Bhadhadhara Kirti , Bharti Neeraj , Kasibhatla Sunitha Manjari , Sonavane Uddhavesh , Joshi Rajendra
Published: July 2021

GenoVault is a cloud-based repository for handling Next Generation Sequencing (NGS) data. It is developed using OpenStack-based private cloud with various services like keystone for authentication, cinder for block storage, neutron for networking and nova for managing compute instances for the Cloud. GenoVault uses object-based storage, which enables data to be stored as objects instead of files or blocks for faster retrieval from different distributed object nodes. Along with a web-based interface, a JavaFX-based desktop client has also been developed to meet the requirements of large file uploads that are usually seen in NGS datasets. Users can store files in their respective object-based storage areas and the metadata provided by the user during file uploads is used for querying the database. GenoVault repository is designed taking into account future needs and hence can scale both vertically and horizontally using OpenStack-based cloud features. Users have an option to make the data shareable to the public or restrict the access as private. Data security is ensured as every container is a separate entity in object-based storage architecture which is also supported by Secure File Transfer Protocol (SFTP) for data upload and download. The data is uploaded by the user in individual containers that include raw read files (fastq), processed alignment files (bam, sam, bed) and the output of variation detection (vcf). GenoVault architecture allows verification of the data in terms of integrity and authentication before making it available to collaborators as per the user’s permissions. GenoVault is useful for maintaining the organization-wide NGS data generated in various labs which is not yet published and submitted to public repositories like NCBI. GenoVault also provides support to share NGS data among the collaborating institutions. GenoVault can thus manage vast volumes of NGS data on any OpenStack-based private cloud.
IL-7 and CCL19-secreting CAR-T cell therapy for tumors with positive glypican-3 or mesothelin
Authors: Pang Nengzhi , Shi Jingxuan , Qin Le , Chen Aiming , Tang Yuou , Yang Hainan , Huang Yufeng , Wu Qingde , Li Xufeng , He Bingjia , Li Tianheng , Liang Baoxia , Zhang Jinglin , Cao Bihui , Liu Manting , Feng Yunfei , Ye Xiaodie , Chen Xiaopei , Wang Lu , Tian Yu , Li Hao , Li Junping , Hu Hong , He Jingping , Hu Yuling , Zhi Cheng , Tang Zhaoyang , Gong Yibo , Xu Fangting , Xu Linfeng , Fan Weijun , Zhao Ming , Chen Deji , Lian Hui , Yang Lili , Li Peng , Zhang Zhenfeng
Published: July 2021

Although chimeric antigen receptor (CAR)-engineered T cells have shown great success in the treatment of B cell malignancies, this strategy has limited efficacy in patients with solid tumors. In mouse CAR-T cells, IL-7 and CCL19 expression have been demonstrated to improve T cell infiltration and CAR-T cell survival in mouse tumors. Therefore, in the current study, we engineered human CAR-T cells to secrete human IL-7 and CCL19 (7 × 19) and found that these 7 × 19 CAR-T cells showed enhanced capacities of expansion and migration in vitro. Furthermore, 7 × 19 CAR-T cells showed superior tumor suppression ability compared to conventional CAR-T cells in xenografts of hepatocellular carcinoma (HCC) cell lines, primary HCC tissue samples and pancreatic carcinoma (PC) cell lines. We then initiated a phase 1 clinical trial in advanced HCC/PC/ovarian carcinoma (OC) patients with glypican-3 (GPC3) or mesothelin (MSLN) expression. In a patient with advanced HCC, anti-GPC3-7 × 19 CAR-T treatment resulted in complete tumor disappearance 30 days post intratumor injection. In a patient with advanced PC, anti-MSLN-7 × 19 CAR-T treatment resulted in almost complete tumor disappearance 240 days post-intravenous infusion. Our results demonstrated that the incorporation of 7 × 19 into CAR-T cells significantly enhanced the antitumor activity against human solid tumor. Trial registration: NCT03198546. Registered 26 June 2017, https://clinicaltrials.gov/ct2/show/NCT03198546?term=NCT03198546&draw=2&rank=1
Cellular senescence or stemness: hypoxia flips the coin
Authors: Otero-Albiol Daniel , Carnero Amancio
Published: July 2021

Cellular senescence is a complex physiological state whose main feature is proliferative arrest. Cellular senescence can be considered the reverse of cell immortalization and continuous tumor growth. However, cellular senescence has many physiological functions beyond being a putative tumor suppressive trait. It remains unknown whether low levels of oxygen or hypoxia, which is a feature of every tissue in the organism, modulate cellular senescence, altering its capacity to suppress the limitation of proliferation. It has been observed that the lifespan of mammalian primary cells is increased under low oxygen conditions. Additionally, hypoxia promotes self-renewal and pluripotency maintenance in adult and embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs) and cancer stem cells (CSCs). In this study, we discuss the role of hypoxia facilitating senescence bypass during malignant transformation and acquisition of stemness properties, which all contribute to tumor development and cancer disease aggressiveness.
Clinical practice recommendations on the management of perioperative cardiac arrest: A report from the PERIOPCA Consortium
Authors: Chalkias Athanasios , Mongardon Nicolas , Boboshko Vladimir , Cerny Vladimir , Constant Anne-Laure , De Roux Quentin , Finco Gabriele , Fumagalli Francesca , Gkamprela Eleana , Legriel Stéphane , Lomivorotov Vladimir , Magliocca Aurora , Makaronis Panagiotis , Mamais Ioannis , Mani Iliana , Mavridis Theodoros , Mura Paolo , Ristagno Giuseppe , Sardo Salvatore , Papagiannakis Nikolaos , Xanthos Theodoros ,   for the PERIOPCA Consortium, Chalkias Athanasios , Mongardon Nicolas , Boboshko Vladimir , Cerny Vladimir , Constant Anne-Laure , De Roux Quentin , Finco Gabriele , Fumagalli Francesca , Gkamprela Eleana , Legriel Stéphane , Lomivorotov Vladimir , Magliocca Aurora , Makaronis Panagiotis , Mamais Ioannis , Mani Iliana , Mavridis Theodoros , Mura Paolo , Ristagno Giuseppe , Sardo Salvatore , Papagiannakis Nikolaos , Xanthos Theodoros
Published: July 2021

Background

Perioperative cardiac arrest is a rare complication with an incidence of around 1 in 1400 cases, but it carries a high burden of mortality reaching up to 70% at 30 days. Despite its specificities, guidelines for treatment of perioperative cardiac arrest are lacking. Gathering the available literature may improve quality of care and outcome of patients.

Methods

The PERIOPCA Task Force identified major clinical questions about the management of perioperative cardiac arrest and framed them into the therapy population [P], intervention [I], comparator [C], and outcome [O] (PICO) format. Systematic searches of PubMed, Embase, and the Cochrane Library for articles published until September 2020 were performed. Consensus-based treatment recommendations were created using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system. The strength of consensus among the Task Force members about the recommendations was assessed through a modified Delphi consensus process.

Results

Twenty-two PICO questions were addressed, and the recommendations were validated in two Delphi rounds. A summary of evidence for each outcome is reported and accompanied by an overall assessment of the evidence to guide healthcare providers.

Conclusions

The main limitations of our work lie in the scarcity of good quality evidence on this topic. Still, these recommendations provide a basis for decision making, as well as a guide for future research on perioperative cardiac arrest.
Asystolic cardiac arrest following liposomal amphotericin B infusion: anaphylaxis or compliment activation-related pseudoallergy?
Authors: Drewett George P. , Copaescu Ana , DeLuca Joseph , Holmes Natasha E. , Trubiano Jason A.
Published: July 2021

Allergic reaction to liposomal amphotericin B is rare. We report a case of cardiac arrest in a 64-year-old woman following liposomal amphotericin B infusion, requiring resuscitation. We also present the results of subsequent skin prick and intradermal testing to liposomal amphotericin on the patient and three healthy controls, highlighting the need for further research into the immunopathogenesis of this reaction.
Acute poisoning with acetamiprid: a case report
Authors: Pirasath Selladurai , Senthuran Rajaram , Athirayan Chandrakulasegeran , Gevakaran Mathyasekeran , Guruparan Mahesan , Gnanathasan Ariaranee
Published: July 2021

Background

Acetamiprid is a potent new first-generation neonicotinoid insecticide in agricultural practices. It is well described that it has low toxicity among animals and is lethal if consumed in large amounts. However, toxicity in humans is rarely reported in literature. Here, we describe acetamiprid toxicity complicated with severe lactic acidosis, myocardial ischemia, refractory hypotension, and severe hypokalemia in a middle-aged man who presented with deliberate self-harming with acetamiprid poisoning in Sri Lanka.

Case presentation

We describe a case of acute poisoning with an acetamiprid in a middle-aged Sri Lankan Tamil farmer for suicidal purposes following family conflicts with his wife. He presented with severe nausea, vomiting, and altered level of consciousness. He had electrocardiogram changes, hypoxia, and lactic acidosis. With intensive care management including ventilatory support, inotropic therapy along with intraarterial blood pressure monitoring, correction of acidosis, and administration of electrolytes, he made good clinical recovery. He was discharged without any further complications 6 days after ingestion of acetamiprid.

Conclusions

This case illustrates a rare, acute poisoning with acetamiprid in human, as well as its clinical manifestations and successful management with supportive therapy. This will be helpful for clinicians to identify clinical manifestations and to guide management of acute poisoning with acetamiprid in the future.
Zoster-associated limb paralysis mimicking acute stroke: a case report
Authors: Dalugama Chamara , Jayasinghe Ruwanthi , Rathnayaka Nimanthi , Medagama Arjuna
Published: July 2021

Background

Varicella zoster virus is a Deoxyribonucleic acid (DNA) virus exclusively affecting humans. Reactivation of varicella zoster virus causes herpes zoster with vesicular eruptions in a restricted dermatomal distribution. Peripheral motor neuropathy is a very rare complication of varicella zoster virus.

Case presentation

A 57-year-old previously well Sri Lankan female presented with acute onset painful weakness of the left upper limb with a preceding history of a febrile illness. Subsequently she developed vesicular eruptions in the dermatomal distribution of cervical 5, 6, and 7. Electromyography was suggestive of acute denervation of cervical 5, 6, and 7 myotomes. Diagnosis of zoster-associated brachial plexopathy was made, and the patient was treated with acyclovir, steroids, and analgesics. She made a good recovery.

Conclusion

Brachial plexus neuritis due to varicella zoster infection should be considered in an acute monoparesis of a limb as it is a treatable and reversible condition
Potential advantages and limitations of using information fusion in media forensics—a discussion on the example of detecting face morphing attacks
Authors: Kraetzer Christian , Makrushin Andrey , Dittmann Jana , Hildebrandt Mario
Published: July 2021

Information fusion, i.e., the combination of expert systems, has a huge potential to improve the accuracy of pattern recognition systems. During the last decades, various application fields started to use different fusion concepts extensively. The forensic sciences are still hesitant if it comes to blindly applying information fusion. Here, a potentially negative impact on the classification accuracy, if wrongly used or parameterized, as well as the increased complexity (and the inherently higher costs for plausibility validation) of fusion is in conflict with the fundamental requirements for forensics.

The goals of this paper are to explain the reasons for this reluctance to accept such a potentially very beneficial technique and to illustrate the practical issues arising when applying fusion. For those practical discussions the exemplary application scenario of morphing attack detection (MAD) is selected with the goal to facilitate the understanding between the media forensics community and forensic practitioners.

As general contributions, it is illustrated why the naive assumption that fusion would make the detection more reliable can fail in practice, i.e., why fusion behaves in a field application sometimes differently than in the lab. As a result, the constraints and limitations of the application of fusion are discussed and its impact to (media) forensics is reflected upon.

As technical contributions, the current state of the art of MAD is expanded by:

The introduction of the likelihood-based fusion and an fusion ensemble composition experiment to extend the set of methods (majority voting, sum-rule, and Dempster-Shafer Theory of evidence) used previously

The direct comparison of the two evaluation scenarios “MAD in document issuing” and “MAD in identity verification” using a realistic and some less restrictive evaluation setups

A thorough analysis and discussion of the detection performance issues and the reasons why fusion in a majority of the test cases discussed here leads to worse classification accuracy than the best individual classifier
Pregnancy complications, substance abuse, and prenatal care predict birthweight in adolescent mothers
Authors: Hacker Miriam , Firk Christine , Konrad Kerstin , Paschke Kerstin , Neulen Joseph , Herpertz-Dahlmann Beate , Dahmen Brigitte
Published: July 2021

Background

Reduced birthweight is associated with adverse physical and mental health outcomes later in life. Children of adolescent mothers are at higher risk for reduced birthweight. The current study aimed to identify the key risk factors affecting birthweight in a well-characterized sample of adolescent mothers to inform preventive public health efforts.

Methods

Sixty-four adolescent mothers (≤ 21 years of age) provided detailed data on pregnancy, birth and psychosocial risk. Separate regression analyses with (1) birthweight and (2) low birthweight (LBW) as outcomes, and pregnancy complications, prenatal care, maternal age, substance abuse during pregnancy, socioeconomic risk, stressful life events and the child’s sex as independent variables were conducted. Exploratively, a receiver operating characteristic (ROC) analysis was performed to investigate the quality of the discriminatory power of the risk factors.

Results

The following variables explained variance in birthweight significantly: prenatal care attendance (p = .006), pregnancy complications (p = .006), and maternal substance abuse during pregnancy (p = .044). Prenatal care attendance (p = .023) and complications during pregnancy (p = .027) were identified as significant contributors to LBW. Substance abuse (p = .013), pregnancy complications (p = .022), and prenatal care attendance (p = .044) showed reasonable accuracy in predicting low birthweight in the ROC analysis.

Conclusions

Among high-risk adolescent mothers, both biological factors, such as pregnancy complications, and behavioural factors amenable to intervention, such as substance abuse and insufficient prenatal care, seem to contribute to reduced birthweight in their children, a predisposing factor for poorer health outcomes later in life. More tailored intervention programmes targeting the specific needs of this high-risk group are needed.
Determinants of diabetic retinopathy in Tikur Anbessa Hospital, Ethiopia: a case–control study
Authors: Seid Kalid , Tesfaye Temamen , Belay Admasu , Mohammed Hayat
Published: July 2021

Background

Diabetic retinopathy is the most frequent complication of Diabetes Mellitus and remains the leading cause of preventable blindness. However, there are limited studies on the determinants of diabetic retinopathy in the study area as well in Ethiopia. Hence, this study aimed to assess the determinants of diabetic retinopathy among diabetic patients at Tikur Anbessa Hospital.

Methods

An institution-based unmatched case–control study design was conducted at Tikur Anbessa Hospital from May 11 to June 26, 2020. Diabetic patients who developed retinopathy within 2 years were cases in the study. Patients who were free of retinopathy were controls in this study. Data were collected using a pretested interviewer-administered questionnaire, Topcon retinal examination, and a record review. The collected data were entered into Epi Data version 3.1 software, and analyzed using SPSS version 25. Binary logistic regression analysis was used to assess the determinants of diabetic retinopathy.

Results

A total of 282 patients (142 cases and 140 controls) were included in the study. The mean age (± Standard deviation) for the cases and the controls were 50.6 (SD: ± 18.7) and 44.9 (SD: ± 17.65) respectively. Patients who had a glucometer at home (AOR = 0.048; 95% CI: 0.005–0.492), exercise adherence (AOR = 0.075; 95% CI: 0.007–0.84), diabetes duration < 5 years (AOR = 0.005; 95% CI: 0.00–0.10) and 5–10 years (AOR = 0.041; 95% CI: 0.003–0.57), health information on diabetic complications (AOR = 0.002; 95% CI: 0.00–0.042) and appointments every month (AOR = 0.004; 95% CI: 0.00–0.073) and every 3 months (AOR = 0.022; 95% CI: 0.002–0.23) were less likely to develop diabetic retinopathy. Participants who had poor glycemic control (AOR = 19.9; 95% CI: 2.34–168.69), systolic hypertension (AOR = 23.4; 95% CI: 2.56–215.36) and nephropathy (AOR = 17.85; 95% CI: 2.01–158.1), had a higher risk of developing diabetic retinopathy.

Conclusions

Patients who had a glucometer at home, exercise adherence, diabetes duration < 10 years, health information on diabetic complications, and frequent follow-up had a preventive role. However, poor glycemic control, systolic hypertension, and nephropathy increase the risk of diabetic retinopathy. A concerted effort should be made to improve the health status of patients with Diabetes Mellitus, with particular emphasis on lifestyle modification practices to prevent diabetic retinopathy.
A comprehensive approach for microbiota and health monitoring in mouse colonies using metagenomic shotgun sequencing
Authors: Scavizzi Ferdinando , Bassi Cristian , Lupini Laura , Guerriero Paola , Raspa Marcello , Sabbioni Silvia
Published: July 2021

Background

Health surveillance of murine colonies employed for scientific purposes aim at detecting unwanted infection that can affect the well-being of animals and personnel, and potentially undermine scientific results. In this study, we investigated the use of a next-generation sequencing (NGS) metagenomic approach for monitoring the microbiota composition and uncovering the possible presence of pathogens in mice housed in specific pathogen-free (SPF) or conventional (non-SPF) facilities.

Results

Analysis of metagenomic NGS assay through public and free algorithms and databases allowed to precisely assess the composition of mouse gut microbiome and quantify the contribution of the different microorganisms at the species level. Sequence analysis allowed the uncovering of pathogens or the presence of imbalances in the microbiota composition. In several cases, fecal pellets taken from conventional facilities were found to carry gene sequences from bacterial pathogens (Helicobacter hepaticus, Helicobacter typhlonius, Chlamydia muridarum, Streptococcus pyogenes, Rodentibacter pneumotropicus, Citrobacter rodentium, Staphylococcus aureus), intestinal protozoa (Entamoeba muris, Tritrichomonas muris, Spironucleus muris) nematoda (Aspiculuris tetraptera, Syphacia obvelata), eukaryotic parasites (Myocoptes musculinus) and RNA virus (Norwalk virus). Thus, the use of NGS metagenomics can reduce the number of tests required for the detection of pathogens and avoid the use of sentinel mice.

Conclusions

In summary, in comparison with standard approaches, which require multiple types of test, NGS assay can detect bacteria, fungi, DNA and RNA viruses, and eukaryotic parasites from fecal pellets in a single test. Considering the need to protect animal well-being and to improve the success and reproducibility of preclinical studies, this work provides the proof-of-concept that the use of NGS metagenomics for health monitoring of laboratory mice is a feasible and dependable approach, that is able to broaden the current concept of health monitoring of laboratory mice from “pathogen surveillance” to a more inclusive “microbiota surveillance”.
E3 ubiquitin ligases: styles, structures and functions
Authors: Yang Quan , Zhao Jinyao , Chen Dan , Wang Yang
Published: July 2021

E3 ubiquitin ligases are a large family of enzymes that join in a three-enzyme ubiquitination cascade together with ubiquitin activating enzyme E1 and ubiquitin conjugating enzyme E2. E3 ubiquitin ligases play an essential role in catalyzing the ubiquitination process and transferring ubiquitin protein to attach the lysine site of targeted substrates. Importantly, ubiquitination modification is involved in almost all life activities of eukaryotes. Thus, E3 ligases might be involved in regulating various biological processes and cellular responses to stress signal associated with cancer development. Thanks to their multi-functions, E3 ligases can be a promising target of cancer therapy. A deeper understanding of the regulatory mechanisms of E3 ligases in tumorigenesis will help to find new prognostic markers and accelerate the growth of anticancer therapeutic approaches. In general, we mainly introduce the classifications of E3 ligases and their important roles in cancer progression and therapeutic functions.
Chemotherapy and Targeted Therapy for Patients With Human Epidermal Growth Factor Receptor 2–Negative Metastatic Breast Cancer That is Either Endocrine-Pretreated or Hormone Receptor–Negative: ASCO Guideline Update
Authors: Moy Beverly , Rumble R. Bryan , Come Steven E. , Davidson Nancy E. , Di Leo Angelo , Gralow Julie R. , Hortobagyi Gabriel N. , Yee Douglas , Smith Ian E. , Chavez-MacGregor Mariana , Nanda Rita , McArthur Heather L. , Spring Laura , Reeder-Hayes Katherine E. , Ruddy Kathryn J. , Unger Paul S. , Vinayak Shaveta , Irvin William J. , Armaghani Avan , Danso Michael A. , Dickson Natalie , Turner Sophie S. , Perkins Cheryl L. , Carey Lisa A.
Published: July 2021

PURPOSE

This guideline updates recommendations of the ASCO guideline on chemotherapy and targeted therapy for patients with human epidermal growth factor receptor 2–negative metastatic breast cancer (MBC) that is either endocrine-pretreated or hormone receptor (HR)–negative.

METHODS

An Expert Panel conducted a targeted systematic literature review guided by a signals approach to identify new, potentially practice-changing data that might translate into revised guideline recommendations.

RESULTS

The Expert Panel reviewed abstracts from the literature review and retained 14 articles.

RECOMMENDATIONS

Patients with triple-negative, programmed cell death ligand-1–positive MBC may be offered the addition of immune checkpoint inhibitor to chemotherapy as first-line therapy. Patients with triple-negative, programmed cell death ligand-1–negative MBC should be offered single-agent chemotherapy rather than combination chemotherapy as first-line treatment, although combination regimens may be offered for life-threatening disease. Patients with triple-negative MBC who have received at least two prior therapies for MBC should be offered treatment with sacituzumab govitecan. Patients with triple-negative MBC with germline BRCA mutations previously treated with chemotherapy may be offered a poly (ADP-ribose) polymerase inhibitor rather than chemotherapy. Patients with HR-positive human epidermal growth factor receptor 2–negative MBC for whom chemotherapy is being considered should be offered single–agent chemotherapy rather than combination chemotherapy, although combination regimens may be offered for highly symptomatic or life-threatening disease. Patients with HR-positive MBC with disease progression on an endocrine agent may be offered treatment with either endocrine therapy with or without targeted therapy or single-agent chemotherapy. Patients with HR-positive MBC with germline BRCA mutations no longer benefiting from endocrine therapy may be offered a poly (ADP-ribose) polymerase inhibitor rather than chemotherapy. No recommendation regarding when a patient's care should be transitioned to hospice or best supportive care alone is possible. Additional information is available at www.asco.org/breast-cancer-guidelines .
“I'm Being Forced to Make Decisions I Have Never Had to Make Before”: Oncologists' Experiences of Caring for Seriously Ill Persons With Poor Prognoses and the Dilemmas Created by COVID-19
Authors: Perumalswami Chithra R. , Chen Emily , Martin Carly , Goold Susan D. , De Vries Raymond , Griggs Jennifer J. , Jagsi Reshma
Published: July 2021

PURPOSE:

The COVID-19 pandemic has created a new set of problems for clinicians. This study examines the experiences of oncologists providing care to seriously ill persons near the end of life in the context of the COVID-19 pandemic.

METHODS:

Between January 2020 and August 2020, we conducted semistructured, in-depth individual interviews with 22 purposefully sampled oncologists from practices enrolled in the Michigan Oncology Quality Consortium. Deidentified transcripts of the interviews were examined using thematic analysis.

RESULTS:

Our respondents described several novel problems created by the COVID-19 pandemic, including: (1) ethical challenges, (2) the need to manage uncertainty—physically and emotionally—on the part of both patients and oncologists, and (3) the difficulty of integrating technology and communication for seriously ill persons. These problems were made more complex by features of the pandemic: resource scarcity (and the need to fairly allocate poor resources), delays in care, high levels of fear, and the increased importance of advance care planning. Nonabandonment served as a way to cope with increased stress, and the use of telemedicine became an increasingly important medium of communication.

CONCLUSION:

This study offers an in-depth exploration of the problems faced by oncologists as a result of the COVID-19 pandemic and how they navigated them. Optimal decision making for seriously ill persons with cancer during the COVID-19 pandemic must include open acknowledgment of the ethical challenges involved, the emotions experienced by both patients and their oncologists, and the urgent need to integrate technology with compassionate communication in determining patient preferences.
The Epidemiology and Genetic Analysis of Children With Idiopathic Type 1 Diabetes in the State of Qatar
Authors: Abdel-Karim Tasneem , Haris Basma , Afyouni Houda , Mohammed Shayma , Khalifa Amel , Al-Maadheed Maryam , Zyoud Mahmoud , Elawwa Ahmed , Al-Khalaf Fawziya , Petrovski Goran , Hussain Khalid
Published: July 2021

Context

Idiopathic type 1 diabetes is characterized by the absence of autoantibodies and the underlying mechanisms are not clear.

Objective

We aimed to study the epidemiology, describe the clinical characteristics, and report results of genetic studies in pediatric patients with idiopathic type 1 diabetes.

Methods

This was a prospective study of type 1 diabetes patients attending Sidra Medicine from 2018 to 2020. Autoantibodies (GAD65, IAA, IA-2A, and ZnT8) were measured and genetic testing was undertaken in patients negative for autoantibodies to rule out monogenic diabetes. Demographic and clinical data of patients with idiopathic type 1 diabetes were compared with patients with autoimmune type 1 diabetes.

Results

Of 1157 patients with type 1 diabetes, 63 were antibody-negative. Upon genome sequencing, 4 had maturity onset diabetes of the young (MODY), 2 had Wolfram syndrome, 1 had H syndrome, and 3 had variants of uncertain significance in MODY genes; 53 patients had idiopathic type 1 diabetes. The most common age of diagnosis was 10 to 14 years. C-peptide level was low but detectable in 30 patients (56.6%) and normal in 23 patients (43.4%) The average body mass index was in the normal range and 33% of the patients had a history of diabetic ketoacidosis (DKA).

Conclusion

Four percent of the children had idiopathic type 1 diabetes. There were statistically significant differences in the C-peptide level and insulin requirement between the 2 groups. DKA was less common in the idiopathic group. Mutations in MODY genes suggest the importance of autoantibody testing and genetic screening for known causes of monogenic diabetes in idiopathic type 1 diabetes. The mechanism of idiopathic type 1 diabetes is unknown but could be due to defects in antibody production or due to autoantibodies that are not yet detectable or discovered.
Formin 3 directs dendritic architecture via microtubule regulation and is required for somatosensory nociceptive behavior
Authors: Das Ravi , Bhattacharjee Shatabdi , Letcher Jamin M. , Harris Jenna M. , Nanda Sumit , Foldi Istvan , Lottes Erin N. , Bobo Hansley M. , Grantier Benjamin D. , Mihály József , Ascoli Giorgio A. , Cox Daniel N.
Published: July 2021

Dendrite shape impacts functional connectivity and is mediated by organization and dynamics of cytoskeletal fibers. Identifying the molecular factors that regulate dendritic cytoskeletal architecture is therefore important in understanding the mechanistic links between cytoskeletal organization and neuronal function. We identified Formin 3 (Form3) as an essential regulator of cytoskeletal architecture in nociceptive sensory neurons in Drosophila larvae. Time course analyses reveal that Form3 is cell-autonomously required to promote dendritic arbor complexity. We show that form3 is required for the maintenance of a population of stable dendritic microtubules (MTs), and mutants exhibit defects in the localization of dendritic mitochondria, satellite Golgi, and the TRPA channel Painless. Form3 directly interacts with MTs via FH1-FH2 domains. Mutations in human inverted formin 2 (INF2; ortholog of form3) have been causally linked to Charcot–Marie–Tooth (CMT) disease. CMT sensory neuropathies lead to impaired peripheral sensitivity. Defects in form3 function in nociceptive neurons result in severe impairment of noxious heat-evoked behaviors. Expression of the INF2 FH1-FH2 domains partially recovers form3 defects in MTs and nocifensive behavior, suggesting conserved functions, thereby providing putative mechanistic insights into potential etiologies of CMT sensory neuropathies.