bluuebunny/crossref_metadata_2025 huggingface dataset:
The deadly face of felid killer cells: The cytotoxic proteins and their genes
Authors: Futas Jan , Oppelt Jan , Vychodilova Leona , Burger Pamela , Horin Petr
Published: March 2022

Natural killer cells and cytotoxic T lymphocytes are the main cell populations of the immune system able to directly kill target cells via cytotoxic granules. Different mammalian species may differ in specific features of their pore‐forming protein (perforin) and granule‐bound serine proteases (granzymes). One perforin gene (PRF1) and four genes encoding granzymes A, B, H, and K (GZMA, GZMB, GZMH, GZMK) were identified in the reference genomes of felids. The objective of this work was to characterize the genes PRF1, GZMA and GZMB in a panel of 17 felid species by next‐generation re‐sequencing. A search of available felid genomes (17 species) retrieved the coding sequences of these genes for comparison to our data. Both sets of sequences or their combinations (23 species) were used for phylogenetic and selection analyses. Nucleotide PRF1, GZMA and GZMB sequences showed high similarities between felid species (over 95% identity). All trees derived from coding sequences expressed phylogenetic relationships corresponding to the zoological taxonomy of the Felidae, except GZMA. No effects of positive selection were detected in the genes studied, however, effects of purifying selection were observed for PRF1 and GZMA. The conservation of PRF1 is in agreement with its critical biological function. The differentiation observed between granzyme sub‐families may reflect an adaptation to pathogen variation. The need to maintain important gene functions and at the same time cope with various pathogens may lead to an equilibrium between positive and negative selective pressures acting on GZMB. The within‐species variability in wild felid populations merits further investigation.
Time‐series transcriptomics reveals a drought‐responsive temporal network and crosstalk between drought stress and the circadian clock in foxtail millet
Authors: Yi Fei , Huo Mingyue , Li Jianrui , Yu Jingjuan
Published: March 2022

Drought stress is a serious factor affecting crop growth and production worldwide. The circadian clock has been identified as key to improving regional adaptability of plants. However, our understanding of the contribution of the circadian clock to drought response and the impacts of drought stress on the circadian clock in plants is still limited. To explore the interactions between the circadian clock and drought stress, foxtail millet seedlings were treated with simulated drought (20% polyethylene glycol‐6000) treatment starting at the day (DD) onset zeitgeber time 0 (ZT0, lights on) and at the night (DN) onset zeitgeber time 16 (ZT16, lights off). A high temporal‐resolution transcriptomic investigation was performed using DD and DN samples collected at intervals of 2 or 4 h within a 24‐h drought‐treatment period. Overall, we identified 13 294 drought‐responsive genes (DRGs). Among these DRGs, 7931 were common between DD and DN samples, 2638 were specific to DD, and 2725 were specific to DN. Additionally, we identified 1257 circadian genes, of which 67% were DRGs. Interestingly, with drought treatment starting at the day for 8, 12 or 16 h, the circadian phase shifted to 12 h. We also found that the circadian clock led to different day and night drought‐responsive pathways. The identification of DRG_Clock (DRG and circadian clock) and DRG_NonClock (DRG and not circadian clock) genes provides a reference for selecting candidate drought resistance genes. Our work reveals the temporal drought‐response process and crosstalk between drought stress and the circadian clock in foxtail millet.
Fetal growth, birth size and energetic cost of gestation in southern right whales
Authors: Christiansen Fredrik , Uhart Marcela M , Bejder Lars , Clapham Phil , Ivashchenko Yulia , Tormosov Dmitry , Lewin Nicolás , Sironi Mariano
Published: March 2022

The cost of reproduction greatly affects a species’ life history strategy. Baleen whales exhibit some of the fastest offspring growth rates in the animal kingdom. We quantified the energetic cost of gestation for southern right whales (Eubalaena australis) by combining whaling catch records of pregnant females with photogrammetry data on southern right whale mothers and calves from two breeding grounds in Argentina and Australia. The relationship between calf birth size and maternal length was determined from repeated measurements of individual females before and after giving birth. Fetal growth was determined from generalized linear models fitted to fetal length data from whaling operations between 1961 and 1967. Fetal length was converted to volume and mass, using the volume‐to‐length relationship of newborn southern right whales calves, and published tissue composition and energy content estimates. Fetal maintenance costs (heat of gestation) and the energy content of the placenta were predicted from published relationships and added to the fetal growth cost to calculate the total cost of gestation. Our findings showed that fetal growth rates and birth size increased linearly with maternal length, with calves being born at ∼35% maternal length. Fetal length increased curvilinearly through gestation, which resulted in an exponential increase in fetal volume and mass. Consequently, the cost of gestation was very low during the first (0.1% of total cost) and second trimester (4.9%), but increased rapidly during the last trimester (95.0%). The heat of gestation incurred the highest cost for pregnant females (73.8%), followed by fetal growth (21.2%) and the placental energy content (5.0%).

Key points

Baleen whales exhibit some of the fastest fetal growth rates in the animal kingdom. Despite this, the energetic cost of gestation is largely unknown, as well as the influence of maternal body size on fetal growth rates and calf birth sizes.

We combined historical whaling records and drone photogrammetry data to determine fetal growth rates and birth sizes in southern right whales (Eubalaena australis), from which we estimated the cost of gestation.

Calf birth size, and consequent fetal growth rates, increased positively with maternal body size.

The cost of gestation was negligible for southern right whale females during the first two trimesters, but increased rapidly during the last trimester.

These results show that late gestation incurs a significant cost for baleen whale females, and needs to be accounted for in bioenergetic models.
Comparative studies of cold/hot probe techniques for accurate plasma measurements
Authors: Li Jian-quan , Zhang Qing-he , Xing Zan-yang , Lu Wen-qi
Published: March 2022

The emissive probe technique and the cold Langmuir probe technique for the plasma potential measurement are compared in microwave electron cyclotron resonance plasmas. With different results of plasma potential, discrepant results of electron temperature and electron density are obtained from a hot emissive probe I–V curve and a cold Langmuir probe I–V curve, respectively. A comparison of the experimental data shows that the plasma parameters obtained from the cold Langmuir probe I–V curve are always grossly underestimated, while the results determined from the hot emissive probe I–V curve are much more reliable. Additionally, based on the experimental results, a novel emissive probe technique named the hot probe with zero emission limit method is proposed to easily obtain the accurate plasma potential and other reliable plasma parameters.
Phase evolution and morphology in Cu-In-Ga sputtered precursors
Authors: Lam Isaac K. , Moon Kyeongchan , Soltanmohammad Sina , Hanket Gregory M. , Kyoung Kim Woo , Shafarman William N.
Published: March 2022

The reaction of metallic precursors has become the primary method of industrial manufacturing for Cu(In,Ga)Se2. Commonly used Cu3Ga sputter targets have thus far dictated that the relative Ga composition of these precursors is Ga/(In+Ga) ≈ 0.25. Cu-In-Ga precursors are prepared with varying DC sputtering conditions and Ga compositions ranging from 0 ≤ Ga/(In+Ga) ≤ 0.75. The phase evolution and morphology of these precursors is characterized using x-ray diffraction (XRD) and scanning electron microscopy, including in situ annealing of precursors during XRD measurements. It is observed that the Ga composition of as-deposited precursors affects phase evolution with annealing. Consistent morphology changes were not observed with changing Ga, however, film morphology was controlled by adjusting In sputter conditions.
A reversal of the song advantage in vocal pitch imitation
Authors: Pfordresher Peter Q.
Published: March 2022

Previous experiments have documented an advantage for vocal pitch-matching when participants sing back a short melody, in contrast to when participants attempt to imitate the pitch contour of spoken English. These results appear to confirm recent claims that music involves greater precision of pitch than speech. A re-analysis of these data is reported here that focuses on imitation of pitch trajectories within sung notes or spoken syllables. When analyzed this way, the domain-based difference reverses and speech imitation exhibits an advantage relative to song imitation. These results suggest that domain-specific advantages in imitation vary as a function of timescale.
Feasibility of Volitional Reaction Time Tests in Athletes: A Systematic Review
Authors: Janicijevic Danica , Garcia-Ramos Amador
Published: March 2022

This systematic review aimed to synthesize the current evidence on the feasibility of volitional reaction time (RT) tests to evaluate the information processing abilities of athletes. Four databases were searched, and, finally, 38 studies exploring the reliability, validity, or sensitivity of RT tests were included. Seven studies explored the reliability, which ranged from poor to excellent, while only three studies explored the validity of RT tests. The most important downside of the majority of the implemented RT tests is their nonspecific nature (i.e., stimulus and response did not resemble the sports actions). Sports scientists should focus on developing RT tests that are specific for each sport and refine the testing procedures to obtain accurate, reproducible, and sensitive measurements of RT.
De novo creation of a naked eye–detectable fluorescent molecule based on quantum chemical computation and machine learning
Authors: Sumita Masato , Terayama Kei , Suzuki Naoya , Ishihara Shinsuke , Tamura Ryo , Chahal Mandeep K. , Payne Daniel T. , Yoshizoe Kazuki , Tsuda Koji
Published: March 2022

Designing fluorescent molecules requires considering multiple interrelated molecular properties, as opposed to properties that straightforwardly correlated with molecular structure, such as light absorption of molecules. In this study, we have used a de novo molecule generator (DNMG) coupled with quantum chemical computation (QC) to develop fluorescent molecules, which are garnering significant attention in various disciplines. Using massive parallel computation (1024 cores, 5 days), the DNMG has produced 3643 candidate molecules. We have selected an unreported molecule and seven reported molecules and synthesized them. Photoluminescence spectrum measurements demonstrated that the DNMG can successfully design fluorescent molecules with 75% accuracy (
n
= 6/8) and create an unreported molecule that emits fluorescence detectable by the naked eye.
Blocking UBE2N abrogates oncogenic immune signaling in acute myeloid leukemia
Authors: Barreyro Laura , Sampson Avery M. , Ishikawa Chiharu , Hueneman Kathleen M. , Choi Kwangmin , Pujato Mario A. , Chutipongtanate Somchai , Wyder Michael , Haffey Wendy D. , O’Brien Eric , Wunderlich Mark , Ramesh Vighnesh , Kolb Ellen M. , Meydan Cem , Neelamraju Yaseswini , Bolanos Lyndsey C. , Christie Susanne , Smith Molly A. , Niederkorn Madeline , Muto Tomoya , Kesari Santosh , Garrett-Bakelman Francine E. , Bartholdy Boris , Will Britta , Weirauch Matthew T. , Mulloy James C. , Gul Zartash , Medlin Stephen , Kovall Rhett A. , Melnick Ari M. , Perentesis John P. , Greis Kenneth D. , Nurmemmedov Elmar , Seibel William L. , Starczynowski Daniel T.
Published: March 2022

Dysregulation of innate immune signaling pathways is implicated in various hematologic malignancies. However, these pathways have not been systematically examined in acute myeloid leukemia (AML). We report that AML hematopoietic stem and progenitor cells (HSPCs) exhibit a high frequency of dysregulated innate immune-related and inflammatory pathways, referred to as oncogenic immune signaling states. Through gene expression analyses and functional studies in human AML cell lines and patient-derived samples, we found that the ubiquitin-conjugating enzyme UBE2N is required for leukemic cell function in vitro and in vivo by maintaining oncogenic immune signaling states. It is known that the enzyme function of UBE2N can be inhibited by interfering with thioester formation between ubiquitin and the active site. We performed in silico structure-based and cellular-based screens and identified two related small-molecule inhibitors UC-764864/65 that targeted UBE2N at its active site. Using these small-molecule inhibitors as chemical probes, we further revealed the therapeutic efficacy of interfering with UBE2N function. This resulted in the blocking of ubiquitination of innate immune- and inflammatory-related substrates in human AML cell lines. Inhibition of UBE2N function disrupted oncogenic immune signaling by promoting cell death of leukemic HSPCs while sparing normal HSPCs in vitro. Moreover, baseline oncogenic immune signaling states in leukemic cells derived from discrete subsets of patients with AML exhibited a selective dependency on UBE2N function in vitro and in vivo. Our study reveals that interfering with UBE2N abrogates leukemic HSPC function and underscores the dependency of AML cells on UBE2N-dependent oncogenic immune signaling states.
Bacillus thuringiensis Cry1Ac Protoxin and Activated Toxin Exert Differential Toxicity Due to a Synergistic Interplay of Cadherin with ABCC Transporters in the Cotton Bollworm
Authors: Liao Chongyu , Jin Minghui , Cheng Ying , Yang Yongbo , Soberón Mario , Bravo Alejandra , Liu Kaiyu , Xiao Yutao
Published: March 2022

Better understanding of the mode of action of
Bacillus thuringiensis
toxins is beneficial for the sustainable application of Bt crops. It is generally accepted that Cry-protoxins need to be activated by proteases to bind with midgut cell proteins and exert toxicity against insects.
Increased Sensitivity of SARS-CoV-2 to Type III Interferon in Human Intestinal Epithelial Cells
Authors: Metz-Zumaran Camila , Kee Carmon , Doldan Patricio , Guo Cuncai , Stanifer Megan L. , Boulant Steeve
Published: March 2022

SARS-CoV-2 infection is not restricted to the respiratory tract and a large number of COVID-19 patients experience gastrointestinal distress. Interferons are key molecules produced by the cell to combat virus infection.
Genome Sequences of Bacteriophages UPEC01, UPEC03, UPEC06, and UPEC07 Infecting Avian Pathogenic Escherichia coli
Authors: Kazibwe George , Ndekezi Christian , Alinaitwe Ruth , Alafi Stephen , Nanteza Ann , Kimuda Magambo Phillip , Nakavuma Jesca Lukanga
Published: March 2022

Here, we present the genome sequences of four bacteriophages that infect avian pathogenic
Escherichia coli
. The phages were isolated from raw sewage in Kampala, Uganda. The genome sizes of the phages ranged between 143,140 bp and 178,307 bp, with an average G+C content of 41.25%.
In Vitro
Activity of Cefiderocol against U.S. and European Gram-Negative Clinical Isolates Collected in 2020 as Part of the SENTRY Antimicrobial Surveillance Program
Authors: Shortridge Dee , Streit Jennifer M. , Mendes Rodrigo , Castanheira Mariana
Published: March 2022

Cefiderocol is the first siderophore-conjugated cephalosporin approved for use in the treatment of human bacterial infections. Cefiderocol has broad-spectrum Gram-negative activity against difficult-to-treat bacterial pathogens that can cause serious infections.
Reducing prescribing errors: making electronic prescribing work for cystic fibrosis inpatients
Authors: Vittery Emma Rebecca , Bayliss Emily , Heed Andrew , Fagan Claire , Thomas Matthew , Tse Yincent
Published: March 2022

Children admitted to our hospital with cystic fibrosis had frequent medication errors due to polypharmacy and addition of specialist and high-risk medications despite an electronic prescribing and medicines administration system in place. We describe a multidisciplinary quality improvement project that combined a computerised order entry system (CPOE) with human factor process changes. Over 12 months, our run chart showed a 43% reduction in prescription errors. For medications prescribable via the CPOE, errors reaching the patient reduced from 50% to 29%. Electronic prescribing can be seen by clinicians as a fixed unalterable system contributing to rather than ameliorating errors. Improving safety requires whole team engagement and working closely with programmers to adapt function and influence human factors.
Case of acquired haemophilia a in Southeast Asia following COVID-19 vaccine
Authors: Ai Vuen Lee , Aun Su-Yin Evelyn , Naila Kori Ahlam , Shah TM
Published: March 2022

Acquired haemophilia A (AHA) is a rare bleeding disorder with high morbidity and mortality, but it is eminently treatable if diagnosis and treatment are prompt. We report a case of AHA in Southeast Asia following the administration of the Pfizer-BioNTech COVID-19 vaccine. A man in his 80s developed multiple bruises 2 weeks after his first dose of the COVID-19 vaccine. Diagnosis was delayed due to his cognitive impairment and low clinical suspicion. This led to a representation with worsening ecchymosis, a left thigh haematoma and symptomatic anaemia. Laboratory testing was notable for an isolated prolongation of the activated partial thromboplastin time, which remained uncorrected in the mixing test. Further testing confirmed the presence of factor VIII (FVIII) inhibitors and low FVIII titres of 6.7%. He responded to treatment with intravenous methylprednisolone and recombinant activated FVII. Screening for autoimmune diseases and malignancies was negative.
Non-specificity of symptoms in infantile-onset Pompe disease may delay the diagnosis and institution of treatment
Authors: Senarathne Udara Dilrukshi , Jasinge Eresha , Viknarajah Mohan Sarojini , Waidyanatha Samantha
Published: March 2022

Pompe disease is an autosomal-recessive inherited disorder of glycogen metabolism due to lysosomal acid alpha-glucosidase deficiency. The infantile-onset form is rapidly fatal if left untreated and presents with respiratory symptoms, a typical encounter during infancy. We discuss two infants presenting with respiratory symptoms since early infancy and found to have cardiomegaly, hypotonia, elevated muscle enzymes, leading to the diagnosis of Pompe disease with genetic confirmation. However, both infants expired before the enzyme replacement therapy due to complications of irreversible muscle damage despite supportive medical care. Presentation with respiratory symptoms common during childhood, absence of alarming symptoms such as hypoglycaemia, ketoacidosis or encephalopathy, and relative rarity of Pompe disease can contribute to lapses in the early diagnosis as observed in the index patients. Thus, these cases emphasise the importance of vigilant assessment of common paediatric presentations, which may be presenting symptoms of underlying sinister pathologies.
Bilateral pulmonary embolism and pulmonary infarctions in active ulcerative colitis
Authors: Bromfield Brittany , Schwartz Marc
Published: March 2022

Crohn’s disease and ulcerative colitis are inflammatory bowel diseases (IBDs) and they primarily involve the intestines and confer an increased risk of thromboembolism (TE). Here we report a case of a young man with active ulcerative colitis (UC) who presented with shortness of breath and syncope. He was found on imaging to have an extensive bilateral pulmonary embolism (PE) and right heart strain with associated pulmonary infarctions. The patient was initially managed with a heparin infusion and subsequently transitioned to a direct acting oral anticoagulant (DOAC) with clinical improvement in his symptoms.
Establishing a method to estimate the effect of antimyopia management options on lifetime cost of myopia
Authors: Fricke Tim R , Sankaridurg Padmaja , Naduvilath Thomas , Resnikoff Serge , Tahhan Nina , He Mingguang , Frick Kevin D
Published: March 2022

Background

Informed decisions on myopia management require an understanding of financial impact. We describe methodology for estimating lifetime myopia costs, with comparison across management options, using exemplars in Australia and China.

Methods

We demonstrate a process for modelling lifetime costs of traditional myopia management (TMM=full, single-vision correction) and active myopia management (AMM) options with clinically meaningful treatment efficacy. Evidence-based, location-specific and ethnicity-specific progression data determined the likelihood of all possible refractive outcomes. Myopia care costs were collected from published sources and key informants. Refractive and ocular health decisions were based on standard clinical protocols that responded to the speed of progression, level of myopia, and associated risks of pathology and vision impairment. We used the progressions, costs, protocols and risks to estimate and compare lifetime cost of myopia under each scenario and tested the effect of 0%, 3% and 5% annual discounting, where discounting adjusts future costs to 2020 value.

Results

Low-dose atropine, antimyopia spectacles, antimyopia multifocal soft contact lenses and orthokeratology met our AMM inclusion criteria. Lifetime cost for TMM with 3% discounting was US$7437 (CI US$4953 to US$10 740) in Australia and US$8006 (CI US$3026 to US$13 707) in China. The lowest lifetime cost options with 3% discounting were antimyopia spectacles (US$7280, CI US$5246 to US$9888) in Australia and low-dose atropine (US$4453, CI US$2136 to US$9115) in China.

Conclusions

Financial investment in AMM during childhood may be balanced or exceeded across a lifetime by reduced refractive progression, simpler lenses, and reduced risk of pathology and vision loss. Our methodology can be applied to estimate cost in comparable scenarios.
UK poSt Arthroplasty Follow-up rEcommendations (UK SAFE): what does analysis of linked, routinely collected national data sets tell us about mid-late term revision risk after hip replacement? Retrospective cohort study
Authors: Smith Lindsay K , Garriga Cesar , Kingsbury Sarah R , Pinedo-Villanueva Rafael , Delmestri Antonella , Arden Nigel K , Stone Martin , Conaghan Philip G , Judge Andrew
Published: March 2022

Objective

To identify patients at risk of mid-late term revision of hip replacement to inform targeted follow-up.

Design

Analysis of linked national data sets from primary and secondary care (Clinical Practice Research Datalink (CPRD-GOLD); National Joint Registry (NJR); English Hospital Episode Statistics (HES); Patient-Reported Outcome Measures (PROMs)).

Participants

Primary elective total hip replacement (THR) aged≥18.

Event of interest

Revision surgery≥5 years (mid-late term) after primary THR.

Statistical methods

Cox regression modelling to ascertain risk factors of mid-late term revision. HR and 95% CI assessed association of sociodemographic factors, comorbidities, medication, surgical variables and PROMs with mid-late term revision.

Results

NJR-HES-PROMs data were available from 2008 to 2011 on 142 275 THR; mean age 70.0 years and 61.9% female. CPRD GOLD-HES data covered 1995–2011 on 17 047 THR; mean age 68.4 years, 61.8% female. Patients had minimum 5 years postprimary surgery to end 2016. In NJR-HES-PROMS data, there were 3582 (2.5%) revisions, median time-to-revision after primary surgery 1.9 years (range 0.01–8.7), with 598 (0.4%) mid-late term revisions; in CPRD GOLD, 982 (5.8%) revisions, median time-to-revision 5.3 years (range 0–20), with 520 (3.1%) mid-late term revisions.

Reduced risk of mid-late term revision was associated with older age at primary surgery (HR: 0.96; 95% CI: 0.95 to 0.96); better 6-month postoperative pain/function scores (HR: 0.35; 95% CI: 0.27 to 0.46); use of ceramic-on-ceramic (HR: 0.73; 95% CI: 0.56 to 0.95) or ceramic-on-polyethylene (HR: 0.76; 95% CI: 0.58 to 1.00) bearing surfaces.

Increased risk of mid-late term revision was associated with the use of antidepressants (HR: 1.32; 95% CI: 1.09 to 1.59), glucocorticoid injections (HR: 1.33; 95% CI: 1.06 to 1.67) and femoral head size≥44 mm (HR: 2.56; 95% CI: 1.09 to 6.02)

No association of gender, obesity or Index of Multiple Deprivation was observed.

Conclusion

The risk of mid-late term THR is associated with age at primary surgery, 6-month postoperative pain and function and implant factors. Further work is needed to explore the associations with prescription medications observed in our data.
Interventions to treat post-traumatic stress disorder (PTSD) in vulnerably housed populations and trauma-informed care: a scoping review
Authors: Bennett Alexandria , Crosse Kien , Ku Michael , Edgar Nicole E , Hodgson Amanda , Hatcher Simon
Published: March 2022

Objectives

The goals of this study are to identify and analyse interventions that aim to treat post-traumatic stress disorder (PTSD) and complex PTSD in people who are vulnerably housed and to describe how these treatments have been delivered using trauma-informed care.

Design

Scoping review.

Search strategy

We searched electronic databases including MEDLINE, Embase, PsycINFO, CINAHL, the Cochrane Library, Web of Science and PTSDpubs for published literature up to November 2021 for any studies that examined the treatment of PTSD in adults who were vulnerably housed. Websites of relevant organisations and other grey literature sources were searched to supplement the electronic database search. The characteristics and effect of the interventions were analysed. We also explored how the interventions were delivered and the elements of trauma-informed care that were described.

Results

28 studies were included. We identified four types of interventions: (1) trauma focused psychotherapies; (2) non-trauma psychotherapies; (3) housing interventions and (4) pharmacotherapies. The trauma-informed interventions were small case series and the non-trauma focused therapies included four randomised controlled trials, were generally ineffective. Of the 10 studies which described trauma-informed care the most commonly named elements were physical and emotional safety, the experience of feeling heard and understood, and flexibility of choice. The literature also commented on the difficulty of providing care to this population including lack of private space to deliver therapy; the co-occurrence of substance use; and barriers to follow-up including limited length of stay in different shelters and high staff turnover.

Conclusions

This scoping review identified a lack of high-quality trials to address PTSD in people who are vulnerably housed. There is a need to conduct well designed trials that take into account the unique setting of this population and which describe those elements of trauma-informed care that are most important and necessary.
Contemporary sex differences in mortality among patients with ST-segment elevation myocardial infarction: a systematic review and meta-analysis
Authors: Xi Ziwei , Qiu Hong , Guo Tingting , Wang Yong , Li Jianan , Li Yang , Zheng Jianfeng , Gao R
Published: March 2022

Objectives

To assess the effect of sex differences on short-term and long-term mortality among patients with ST-segment elevation myocardial infarction (STEMI).

Design

Systematic review and meta-analysis of contemporary available evidence.

Setting

PubMed, Embase and Cochrane Library were searched for relevant studies reporting sex-specific outcomes among patients with STEMI published between 1 January 2010 and 1 August 2020. Risk ratios (RRs) and 95% CIs were measured using DerSimonian and Laird random-effects model. Sensitivity analyses were performed and publication bias was also checked. All statistical analyses were performed using STATA V.15.0.

Participants

Studies providing data about short-term or long-term mortality stratified by sex in patients with STEMI were included. Only study conducted in last 10 years were included.

Primary and secondary outcome measures

The primary outcome was all-cause death at short-term (in-hospital or 30 days) and long-term (at least 12 months) follow-up.

Results

A total of 15 studies involving 128 585 patients (31 706 (24.7%) female and 96 879 (75.3%) male) were included. In the unadjusted analyses, female were at a higher risk of short-term mortality (RR, 1.73; 95% CI 1.53 to 1.96, p<0.001, I2=77%) but not long-term mortality (RR, 1.23; 95% CI 0.89 to 1.69, p=0.206, I2=77.5%). When adjusted effect estimates from individual studies were used in meta-analysis, the association between female and higher risk of short-term mortality remained significant (RR, 1.24; 95% CI 1.11 to 1.38, p<0.001, I2=39.6%). And adjusted long-term mortality was also similar between female and male (RR, 1.11; 95% CI 0.42 to 1.80, p=0.670, I2=74.5%).

Conclusions

An increased short-term but not long-term mortality was found in female with STEMI. After adjustment for baseline cardiovascular risk factors and clinical profiles, short-term mortality remains higher in female with STEMI compared with male, indicating the need for further improvements in management in female patients.
Willingness, perceived barriers and motivators in adopting mobile applications for health-related interventions among older adults: a scoping review
Authors: Ahmad Nurul Asilah , Mat Ludin Arimi Fitri , Shahar Suzana , Mohd Noah Shahrul Azman , Mohd Tohit Noorlaili
Published: March 2022

Objectives

This scoping review aims to identify the level of willingness, the existing barriers, and motivators among older adults in using mobile applications to monitor and manage their health conditions. The secondary aim of this paper is to categorise these willingness, barriers and motivators using the Theoretical Domains Framework (TDF).

Design

Scoping review.

Data source

PubMed, Embase, CINAHL, Cochrane Library, Google Scholar and Science Direct (January 2009–December 2020).

Study selection

Studies that describe older adults’ perspectives with regard to their willingness, barriers or motivators towards the use of mobile applications in monitoring and managing their health condition were included.

Data extraction

Titles and abstracts were initially screened by two reviewers. Articles agreed by both reviewers were proceeded to full-text screening. One reviewer extracted the data, which were verified by a second reviewer. Findings were further classified according to the 14 TDF domains by two researchers.

Results

Six studies were included in the final scoping review. Barriers to adopting mobile applications for health-related interventions among older adults were the most common topic identified in the included studies. Barriers included being unaware of the existence of mobile health applications, lack of technological skills, lack of perceived ability and time, absence of professional involvements, and violation of trust and privacy. With regard to willingness, older adults are willing to use mobile applications if the apps incorporated features from a trusted source and have valid credentials. Motivators included continuous improvements of mobile applications’ design interface and personalised features tailored to older adults’ needs.

Conclusions

With the constant research for more diversified technology, the development of mobile applications to help older adults to manage and monitor health is seen as feasible, but barriers have to be addressed. The most prominent barriers linked to TDF domains were: (1) technological skills, (2) belief about consequences, and (3) memory, attention and decision process. Future interventions should use behaviour change techniques that target these three TDF domains in order to improve the ability to engage older adults with mobile technology.
Adolescent stress experiences over time study (ASETS) protocol: design and methods of a prospective longitudinal study of sexual minority adolescents in the USA
Authors: Schrager Sheree M , Mamey Mary Rose , Rhoades Harmony , Goldbach Jeremy T
Published: March 2022

Introduction

Sexual minority adolescents (SMA) report higher rates of anxiety, self-harm, depression and suicide than heterosexual peers. These disparities appear to persist into adulthood and may worsen for certain subgroups, yet the mechanisms that drive these concerns remain poorly understood. Minority stress theory, the predominant model for understanding these disparities, posits that poorer outcomes are due to the stress of living in a violently homophobic and discriminatory culture. Although numerous studies report associations between minority stress and behavioural health in adolescence, no study has comprehensively examined how minority stress may change throughout the course of adolescence, nor how stress trajectories may predict health outcomes during this critical developmental period.

Methods and analysis

Between 15 May 2018 and 1 April 2019, we recruited a US national sample of diverse SMA (n=2558) age 14–17 through social media and respondent-driven sampling strategies. A subset of participants (n=1076) enrolled in the longitudinal component and will be followed each 6 months until 1 July 2022. Primary outcomes include symptoms of depression, anxiety and post-traumatic stress disorder; suicidality and self-harm and substance use. The key predictor is minority stress, operationalised as the Sexual Minority Adolescent Stress Inventory. We will use parallel cohort-sequential latent growth curve models to test study hypotheses within a developmental framework.

Ethics and dissemination

All participants provided assent to participate, and longitudinal participants provided informed consent at the first follow-up survey after reaching age 18. All study procedures were reviewed and approved by the University of Southern California Social–Behavioral Institutional Review Board, including a waiver of parental permission given the potential for harm due to unintentional ‘outing’ to a parent during the consent process. The final anonymous data set will be available on request, and research findings will be disseminated through academic channels and products tailored for the lay community.
National patient groups in Canada and their disclosure of relationships with pharmaceutical companies: a cross-sectional study
Authors: Lexchin Joel , Batt Sharon , Goldberg Devorah , Shnier Adrienne
Published: March 2022

Objectives

This study investigates the information and policies that Canadian patient groups post on their publicly available websites about their relationships with pharmaceutical companies.

Design

Cross-sectional study.

Setting

Canadian national patient groups.

Participants

Ninety-seven patient groups with publicly available websites.

Interventions

Each patient group was contacted by email. Information from patient groups’ websites was collected about: total annual revenue for the latest fiscal year, year revenue was reported, revenue from pharmaceutical company donors, purpose of the donation, presence of donors’ logos on the website and hyperlinks to donors’ websites, previous and current employment information about board members and staff, external audits about the group’s finances and whether the group endorses products made by donors. Analysis of publicly available policies looking at: board and/or advisory board, acceptance of donations and revenue generation, independence of decision-making, endorsements, assistance to and/or interactions between patient members from a donor or another company/person acting on behalf of a donor and audits/monitoring/compliance.

Primary and secondary outcome measures

Number of patient groups posting information on their websites about their relationships with pharmaceutical companies; the presence and contents of patient group policies covering different topics about relationships with pharmaceutical companies.

Results

Fifty-three (54.6%) of 97 groups reported donations from pharmaceutical companies. Forty-one (42.3%) groups showed the logos of pharmaceutical companies on their websites and 22 (53.7%) had hyperlinks to pharmaceutical company websites. Twenty-five (25.8%) of these groups endorsed pharmaceutical products produced by brand-name companies that had donated to the groups. Twenty-six (26.8%) groups had policies that dealt with relationships with pharmaceutical companies.

Conclusions

Pharmaceutical industry funding of the included patient groups was common. Despite this, relatively little information was provided on patient group websites about their relationships with pharmaceutical companies. Only 26 out of 97 groups had publicly available policies that directly dealt with their relationships with pharmaceutical companies.
Interventions for social isolation in older adults who have experienced a fall: a systematic review
Authors: Tricco Andrea C , Thomas Sonia M , Radhakrishnan Amruta , Ramkissoon Naveeta , Mitchell Gary , Fortune Jennifer , Jiang Ying , de Groh Margaret , Anderson Kerry , Barker Joan , Gauthier-Beaupré Amélie , Watt Jennifer , Straus Sharon E
Published: March 2022

Objectives

The objective of our systematic review was to identify the effective interventions to prevent or mitigate social isolation and/or loneliness in older adults who experienced a fall.

Design

Systematic review.

Data sources

MEDLINE, Embase, the Cochrane Central Register of Controlled Trials and Ageline were searched (from inception to February 2020).

Methods

Studies were eligible if they described any intervention for social isolation in older adults living in a community setting who experienced a fall, and reported outcomes related to social isolation or loneliness.

Two independent reviewers screened citations, abstracted data and appraised risk of bias using the Cochrane risk of bias tool. The results were summarised descriptively.

Results

After screening 4069 citations and 55 full-text articles, four studies were included. The four studies varied in study design, including a randomised controlled trial, non-randomised controlled trial, an uncontrolled before-after study and a quasiexperimental study. Interventions varied widely, and included singing in a choir, a patient-centred, interprofessional primary care team-based approach, a multifactorial assessment targeting fall risk, appropriate medication use, loneliness and frailty, and a community-based care model that included comprehensive assessments and multilevel care coordination. Outcome measures varied and included scales for loneliness, social isolation, social interaction, social networks and social satisfaction. Mixed results were found, with three studies reporting no differences in social isolation or loneliness after the intervention. Only the multifactorial assessment intervention demonstrated a small positive effect on loneliness compared with the control group after adjustment (B=−0.18, 95% CI −0.35 to −0.02).

Conclusions

Few studies examined the interventions for social isolation or loneliness in older adults who experienced a fall. More research is warranted in this area.

PROSPERO registration number

CRD42020198487.
Optimal iron content in ready-to-use therapeutic foods for the treatment of severe acute malnutrition in the community settings: a protocol for the systematic review and meta-analysis
Authors: Imdad Aamer , François Melissa , Chen Fanny F , Smith Abigail , Tsistinas Olivia , Tanner-Smith Emily , Das Jai K , Bhutta Zulfiqar Ahmed
Published: March 2022

Introduction

The current standard of care for children with severe acute malnutrition (SAM) involves using ready-to-use therapeutic food (RUTF) to promote growth; however, the precise formulation to achieve optimal recovery remains unclear. Emerging research suggests that alternative RUTF formulations may be more effective in correcting SAM-related complications such as anaemia and iron deficiency. This systematic review commissioned by the WHO aims to synthesise the most recent research on the iron content in RUTF and related products in the community-based treatment of uncomplicated severe malnutrition in children aged 6 months and older.

Methods and analysis

We will search multiple electronic databases. We will include randomised controlled trials and non-randomised studies with a control arm. The intervention group will be infants who received RUTF treatments other than the current recommended guidelines set forth by the WHO. The comparison group is children receiving RUTF containing iron at the current WHO-recommended level of 1.9 mg/100 kcal (10–14 mg/100 g). The primary outcomes of interest include blood haemoglobin concentration, any anaemia, severe anaemia, iron-deficiency anaemia, recovery from SAM and any adverse outcomes. We will use meta-analysis to pool findings if sufficient homogeneity exists among included studies. The risk of bias in studies will be evaluated using the Cochrane risk of bias-2. We will use the Grading of Recommendations Assessment, Development, and Evaluation(GRADE) approach to examine the overall certainty of evidence.

Ethics and dissemination

This is a systematic review and will not involve direct contact with human subjects. The findings of this review will be published in a peer-reviewed journal and will guide the WHO’s recommendation on the optimal iron content in RUTFs for the treatment of SAM in children aged 6–59 months.
Improving the mental health and mental health support available to adolescents with social care-experience via low-intensity life story work: a realist review protocol
Authors: Hammond Simon P , Duddy Claire , Mickleburgh Ella , Hiller Rachel , Neil Elsbeth , Williams Kevin , Rodgers Luke , Wilson Jon , Wong Geoff
Published: March 2022

Introduction

Adolescents are the fastest growing group entering social care and are most at risk of mental ill-health. Life Story Work (LSW) is an existing transdiagnostic intervention thought to improve the well-being and mental health of children and adolescents under the care of a local authority by assisting the processing of trauma. Yet LSW is poorly evidenced, lacks standardisation and focuses on younger children. LSW is also high-intensity, relying on specialist input over several months. Adolescent-focused low-intensity-LSW is a promising alternative. However, there is poor evidence on how LSW, let alone low-intensity-LSW should be delivered to adolescents. We aim to identify why, how, in what contexts, for whom and to what extent low-intensity-LSW interventions can be delivered to adolescents with care-experience.

Methods and analysis

Undertaking a realist review, we will: (1) develop an initial programme theory (PrT) of adolescent-focused low-intensity-LSW by consulting with two key expert panels (care-experienced and professional stakeholders), and by searching the literature to identify existing relevant theories; (2) undertake a comprehensive literature search to identify secondary data to develop and refine our emerging PrT. Searches will be run between 12/2021-06/2022 in databases including MEDLINE, PsycINFO, ASSIA and relevant sources of grey literature; (3) select, extract and organise data; (4) synthesise evidence using a realist logic of analysis and undertake further iterative data searching and consultation with our expert panels; (5) write up and share the refined PrT with our expert panels for their final comments. From this process guidance will be developed to help improve the delivery of LSW to support the mental health needs of adolescents with care-experience.

Ethics and dissemination

Ethical approval is not required. Dissemination will include input from expert panels. We will develop academic, practice and youth focused outputs targeting adolescents, their carers, social, healthcare, and educational professionals, academics, and policymakers.

PROSPERO registration number

CRD42021279816.
Periorbital and orbital cellulitis in children: a survey of emergency physicians and analysis of clinical practice guidelines across the PERUKI network
Authors: Tolhurst-Cleaver Meriel , Evans Jordan , Waterfield Thomas , Adamson Jonathan , Marlow Robin , Lyttle Mark D , Roland Damian
Published: March 2022

Background

Due to limited evidence to guide management of periorbital cellulitis (POC), we surveyed current practice and assessed quality and consistency of local clinical practice guidelines (CPGs) to highlight future research priorities.

Methods

A web-based survey was sent to a designated emergency physician (who clinically assesses children) at Paediatric Emergency Research United Kingdom and Ireland (PERUKI) sites between 23 November 2018 to 22 January 2019. A nominated site lead offered one response as a department-wide perspective on admission, severity assessment, treatment, disposition and specialty consultation request. Sites shared their CPG. These were compared using a standardised data collection tool, and quality assessed using Standardised Reporting Practice Guidelines in Healthcare (RIGHT) criteria. Survey responses were also compared against CPG recommendations.

Results

83% (49/59) institutions invited submitted an individual survey response. 67% of responding sites had a CPG and 63% (31/49) submitted these. CPG quality was poor (mean 6.7/35 RIGHT criteria). 21 different severity markers were identified across CPGs. Most CPGS recommend investigations for severe disease, yet 23% (7/31) advise blood culture universally. 90% of CPGs advise discharge with oral antibiotics for milder cases, yet 86% of respondents reported departmental admission of all patients with POC. Nearly all respondents included proptosis, systemically unwell and visual disturbance as indications for admission but differed regarding importance of other signs.

Conclusions

We demonstrated variation in practice across the PERUKI network in assessment of severity and management of POC. CPGs vary in recommendations, and clinical practice appears to differ from CPGs. Guidelines were generally of poor quality when compared against RIGHT standards.
Comparative whole transcriptome analysis of Parkinson’s disease focusing on the efficacy of zonisamide
Authors: Naito Tatsuhiko , Satake Wataru , Cha Pei-Chieng , Kobayashi Kazuhiro , Murata Miho , Toda Tatsushi
Published: March 2022

Objective

Interindividual variations in responsiveness to zonisamide in patients with Parkinson’s disease (PD) have been observed in clinical settings. To decipher the molecular mechanisms determining the efficacy of zonisamide, we conducted whole transcriptome sequencing analysis of patients with PD.

Methods

We selected 23 super-responders (SRs) and 25 non-responders (NRs) to zonisamide from patients with PD who had participated in a previous clinical trial for the approval of zonisamide for the treatment of ‘wearing-off’. Whole transcriptome analysis of peripheral blood was conducted on samples taken before and 12 weeks after zonisamide treatment. We performed differential gene expression analysis to compare between the SRs and NRs at each time point.

Results

Differentially expressed genes in the pre-treatment samples were significantly enriched for glutamatergic synapses and insulin-like growth factor binding (Padj=7.8 × 10−3and 0.029, respectively). The gene sets associated with these functions changed more dynamically by treatment in SRs than NRs (p=7.2 × 10−3and 8.2 × 10−3, respectively).

Conclusions

Our results suggest that the efficacy of zonisamide in PD patients is associated with glutamate-related synaptic modulation and p53-mediated dopaminergic neural loss. Their transcriptomic differences could be captured before treatment, which would lead to the realisation of future personalised treatment.