bluuebunny/crossref_metadata_2025 huggingface dataset:
Biologic Therapy for Budesonide-refractory, -dependent or -intolerant Microscopic Colitis: a Multicentre Cohort Study from the GETAID
Authors: Boivineau Grégoire , Zallot Camille , Zerbib Franck , Plastaras Laurianne , Amiot Aurélien , Boivineau Lucile , Koch Stéphane , Peyrin-Biroulet Laurent , Vuitton Lucine
Published: July 2022

Background

Budesonide remains the backbone therapy for microscopic colitis [MC]; however, relapses are frequent, and some patients are intolerant or dependent. Anti-TNF therapy is increasingly used to treat these patients, but available evidence is still limited. The aim of this study was to evaluate the effectiveness and safety of anti-TNF therapy in MC patients failing budesonide.

Methods

In a multicentre retrospective cohort study, budesonide-refractory, -dependent, or -intolerant MC patients treated with anti-TNF agents were included. Clinical remission was defined as fewer than three bowel movements per day, and clinical response was defined as an improvement in stool frequency of at least 50%.

Results

Fourteen patients were included. Median age was 58.5 years, median disease duration was 25 months, and median follow-up was 29.5 months. Seven patients were treated with infliximab [IFX], and seven with adalimumab. Clinical remission without steroids at 12 weeks was reached in 5/14 [35.7%] patients; all of these received IFX. Clinical response at 12 and 52 weeks, was obtained in 9/14 [64.3%] and 7/14 [50%] patients, respectively. Five patients switched to another anti-TNF agent. When considering both first- and second-line anti-TNF therapies, 7 [50%] patients were in clinical remission at Week 52. Mild to moderate adverse events were reported in six ptients. Two patients were treated with vedolizumab, of whom one had clinical response; one patient treated with ustekinumab had no response.

Conclusions

This is the first multicentre cohort study showing that half of patients treated with anti-TNF therapy for MC achieved clinical remission in case of budesonide failure.
Cardiac magnetic resonance for prophylactic implantable-cardioverter defibrillator therapy international study: prognostic value of cardiac magnetic resonance-derived right ventricular parameters substudy
Authors: Al’Aref Subhi J , Altibi Ahmed M , Malkawi Abdallah , Mansour Munthir , Baskaran Lohendran , Masri Ahmad , Rahmouni Hind , Abete Raffaele , Andreini Daniele , Aquaro Giovanni , Barison Andrea , Bogaert Jan , Camastra Giovanni , Carigi Samuela , Carrabba Nazario , Casavecchia Grazia , Censi Stefano , Cicala Gloria , Conte Edoardo , De Cecco Carlo N , De Lazzari Manuel , Di Giovine Gabriella , Di Roma Mauro , Dobrovie Monica , Focardi Marta , Gaibazzi Nicola , Gismondi Annalaura , Gravina Matteo , Guglielmo Marco , Lanzillo Chiara , Lombardi Massimo , Lorenzoni Valentina , Lozano-Torres Jordi , Margonato Davide , Martini Chiara , Marzo Francesca , Masci Piergiorgio , Masi Ambra , Memeo Riccardo , Moro Claudio , Mushtaq Saima , Nese Alberto , Palumbo Alessandro , Pavon Anne Giulia , Pedrotti Patrizia , Pepi Mauro , Perazzolo Marra Martina , Pica Silvia , Pradella Silvia , Presicci Cristina , Rabbat Mark G , Raineri Claudia , Rodriguez-Palomares Jose’ F , Sbarbati Stefano , Schoepf U Joseph , Squeri Angelo , Sverzellati Nicola , Symons Rolf , Tat Emily , Timpani Mauro , Todiere Giancarlo , Valentini Adele , Varga-Szemes Akos , Volpe Alessandra , Fusini Laura , Guaricci Andrea Igoren , Schwitter Jurg , Pontone Gianluca
Published: July 2022

Aims

Right ventricular systolic dysfunction (RVSD) is an important determinant of outcomes in heart failure (HF) cohorts. While the quantitative assessment of RV function is challenging using 2D-echocardiography, cardiac magnetic resonance (CMR) is the gold standard with its high spatial resolution and precise anatomical definition. We sought to investigate the prognostic value of CMR-derived RV systolic function in a large cohort of HF with reduced ejection fraction (HFrEF).

Methods and results

Study cohort comprised of patients enrolled in the CarDiac MagnEtic Resonance for Primary Prevention Implantable CardioVerter DefibrillAtor ThErapy registry who had HFrEF and had simultaneous baseline CMR and echocardiography (n = 2449). RVSD was defined as RV ejection fraction (RVEF) <45%. Kaplan–Meier curves and cox regression were used to investigate the association between RVSD and all-cause mortality (ACM). Mean age was 59.8 ± 14.0 years, 42.0% were female, and mean left ventricular ejection fraction (LVEF) was 34.0 ± 10.8. Median follow-up was 959 days (interquartile range: 560–1590). RVSD was present in 936 (38.2%) and was an independent predictor of ACM (adjusted hazard ratio = 1.44; 95% CI [1.09–1.91]; P = 0.01). On subgroup analyses, the prognostic value of RVSD was more pronounced in NYHA I/II than in NYHA III/IV, in LVEF <35% than in LVEF ≥35%, and in patients with renal dysfunction when compared to those with normal renal function.

Conclusion

RV systolic dysfunction is an independent predictor of ACM in HFrEF, with a more pronounced prognostic value in select subgroups, likely reflecting the importance of RVSD in the early stages of HF progression.
Dentoskeletal and soft tissue changes after treatment of crowding with premolar extractions: a 50-year follow-up
Authors: Al-Taai Nameer , Persson Maurits , Ransjö Maria , Levring Jäghagen Eva , Westerlund Anna
Published: July 2022

Background

The long-term effects on dentofacial morphology of interceptive treatment with premolar extractions, in the absence of subsequent orthodontic treatment, have not been fully explored.

Objective

The aim was to investigate the effects of premolar extractions (without subsequent orthodontic treatment) on the dentoskeletal and soft tissue profile of patients aged between 12 and 62 years with Class I malocclusion with severe crowding, as compared to untreated controls.

Materials and methods

The Extraction group (N = 30 with Class I crowding malocclusion) had their first premolars removed in early adolescence without subsequent orthodontic treatment. The Control group included 30 untreated subjects with Class I normal occlusion. Cephalograms were taken at 12 (T1), 15 (T2), 30 (T3), and 62 (T4) years of age. A superimposition-based cephalometric method was used to assess the dentoskeletal and soft tissue changes.

Results

There were no significant differences between the Extraction and Control groups in terms of skeletal sagittal relation, incisor inclination, and protrusion, or most of the soft tissue parameters throughout the observation period. However, significant differences were observed between the groups with respect to the vertical relations in T2–T3, such that the Extraction group showed more-pronounced decreases in the ML/NSL, ML/NL, and Gonial angles and more-pronounced increases in facial heights.

Conclusions and implications

Treatment for subjects with Class I malocclusion with severe crowding by the extraction of four premolars, without subsequent orthodontic treatment, does not affect the long-term dentoskeletal and soft tissue profile, as compared to an untreated Control group. The degree of crowding, rather than changes in dentofacial morphology, is crucial in deciding on extraction therapy.
A comparative analysis of genomic and phenomic predictions of growth-related traits in 3-way coffee hybrids
Authors: Mbebi Alain J , Breitler Jean-Christophe , Bordeaux Mélanie , Sulpice Ronan , McHale Marcus , Tong Hao , Toniutti Lucile , Castillo Jonny Alonso , Bertrand Benoît , Nikoloski Zoran
Published: July 2022

Genomic prediction has revolutionized crop breeding despite remaining issues of transferability of models to unseen environmental conditions and environments. Usage of endophenotypes rather than genomic markers leads to the possibility of building phenomic prediction models that can account, in part, for this challenge. Here, we compare and contrast genomic prediction and phenomic prediction models for 3 growth-related traits, namely, leaf count, tree height, and trunk diameter, from 2 coffee 3-way hybrid populations exposed to a series of treatment-inducing environmental conditions. The models are based on 7 different statistical methods built with genomic markers and ChlF data used as predictors. This comparative analysis demonstrates that the best-performing phenomic prediction models show higher predictability than the best genomic prediction models for the considered traits and environments in the vast majority of comparisons within 3-way hybrid populations. In addition, we show that phenomic prediction models are transferrable between conditions but to a lower extent between populations and we conclude that chlorophyll a fluorescence data can serve as alternative predictors in statistical models of coffee hybrid performance. Future directions will explore their combination with other endophenotypes to further improve the prediction of growth-related traits for crops.
mtDNA content in cumulus cells does not predict development to blastocyst or implantation
Authors: Martínez-Moro Álvaro , Lamas-Toranzo Ismael , González-Brusi Leopoldo , Pérez-Gómez Alba , Padilla-Ruiz Ester , García-Blanco Javier , Bermejo-Álvarez Pablo
Published: July 2022

STUDY QUESTION

Is relative mitochondrial DNA (mtDNA) content in cumulus cells (CCs) related to embryo developmental competence in humans and/or the bovine model?

SUMMARY ANSWER

mtDNA content in CCs provides a poor predictive value of oocyte developmental potential, both in vitro and following embryo transfer.

WHAT IS KNOWN ALREADY

CCs are closely connected to the oocyte through transzonal projections, serving essential metabolic functions during folliculogenesis. These oocyte-supporting cells are removed and discarded prior to ICSI, thereby providing interesting biological material on which to perform molecular analyses designed to identify markers that predict oocyte developmental competence. Previous studies have positively associated oocyte mtDNA content with developmental potential in animal models and women. However, it remains debatable whether mtDNA content in CCs could be used as a proxy to infer oocyte developmental potential

STUDY DESIGN, SIZE, DURATION

mtDNA content was analyzed in CCs obtained from 109 human oocytes unable to develop to blastocyst, able to develop to blastocyst but failing to establish pregnancy or able to develop to blastocyst and to establish pregnancy. mtDNA analysis was also performed on bovine cumulus samples collected from 120 oocytes unable to cleave, oocytes developing into cleaved embryos but arresting development prior to the blastocyst stage or oocytes developing to blastocysts.

PARTICIPANTS/MATERIALS, SETTING, METHODS

Human CCs samples were obtained from women undergoing IVF. Only unfrozen oocytes and embryos not submitted to preimplantation genetic testing were included in the analysis. Bovine samples were obtained from slaughtered cattle and individually matured, fertilized and cultured in vitro. Relative mtDNA was assessed by quantitative PCR analysis.

MAIN RESULTS AND THE ROLE OF CHANCE

mtDNA content in human and bovine CCs did not differ according to the developmental potential of their enclosed oocyte. Moreover, mtDNA content in bovine oocytes did not correlate with that of their corresponding CCs.

LARGE SCALE DATA

N/A.

LIMITATIONS, REASONS FOR CAUTION

The lack of correlation found between mtDNA content in human CCs and oocytes was also assessed in bovine samples. Although bovine folliculogenesis, mono-ovulatory ovulation and early embryo development exhibit considerable similarities with that of humans, they may not be fully comparable.

WIDER IMPLICATIONS OF THE FINDINGS

The use of molecular markers for oocyte developmental potential in CCs could be used to enhance success rates following single embryo transfer. However, our data indicate that mtDNA in CCs is not a good proxy for oocyte quality.

STUDY FUNDING/COMPETING INTEREST(S)

This research was supported by the Industrial Doctorate Project IND2017/BIO-7748 funded by the Madrid Region Government. The authors declare no competing interests.
Divergent Effects of Ocean Warming on Byssal Attachment in Two Congener Mussel Species
Authors: Newcomb L A , Cannistra A F , Carrington E
Published: July 2022

Synopsis

Organisms rely on the integrity of the structural materials they produce to maintain a broad range of processes, such as acquiring food, resisting predators, or withstanding extreme environmental forces. The production and maintenance of these biomaterials, which are often modulated by environmental conditions, can therefore have important consequences for fitness in changing climates. One well-known example of such a biomaterial is mussel byssus, an array of collagen-like fibers (byssal threads) that tethers a bivalve mollusk securely to benthic marine substrates. Byssus strength directly influences mortality from dislodgement, predation, or competition and depends on the quantity and quality of byssal threads produced. We compared the temperature sensitivity of byssal attachment strength of two mussel species common to the west coast of North America, Mytilus trossulus and M. galloprovincialis, when exposed to seawater temperatures ranging from 10 to 24°C in the laboratory. We found that the two species attached equally strong in seawater ≤18°C, but higher temperatures caused byssal thread production rate and quality (break force and extensibility) to be greatly reduced in M. trossulus and increased in M. galloprovincialis, leading to a 2–10-fold difference in overall byssus strength between the two species. Using this threshold value (18°C), we mapped habitat for each species along the west coast of North America based on annual patterns in sea surface temperature. Estimated ranges are consistent with the current distribution of the two species and suggest a potential mechanism by which ocean warming could facilitate the northern expansion of M. galloprovincialis and displacement of native M. trossulus populations.
Neuroimmune crosstalk in the gut and liver
Authors: Teratani Toshiaki , Mikami Yohei , Kanai Takanori
Published: July 2022

It has long been assumed that the nervous system exerts distinct effects on immune functions, given the large number of immune disorders that are affected by mental stress. In fact, many different immune cells have been shown to possess a wide variety of neurotransmitter receptors and receive signals from various neurotransmitters, including acetylcholine and noradrenaline. Compared with the findings on local neuroimmune interactions, limited experimental techniques have so far failed to capture a comprehensive overview of neuroimmune interactions between distant organs and the autonomic nervous system in vivo, and the molecular mechanisms underlying local immune regulation of the nervous system have long remained unclear. However, the recent rapid progress in genetic recombination, microscopy and single-cell analysis has deepened our understanding of the anatomical and physiological functions of peripheral nerves at each organ to which they belong. Furthermore, the development of optogenetic and chemogenetic methods has enabled the artificial modulation of specific neuronal activities, and there has been remarkable progress in elucidation of the interaction between nerves and immune cells in vivo, particularly in barrier organs such as the gastrointestinal tract, respiratory tract and skin. This review focuses on the immunoregulatory mechanisms governed by the autonomic nervous system and outlines the latest findings in the regulation of enteric and hepatic immunity by the nervous system.
On the Analytic Characteristics of Commercial Acetaminophen Assays in the United States
Authors: Ali Khameinei , Chiang William , Wang Josh Jiaxing
Published: July 2022

Background

The management of patients with acetaminophen (APAP) toxicity is largely informed by the blood concentration. We sought to assess the analytical characteristics of past and current commercial APAP assays in the United States.

Methods

We systematically reviewed the analytical characteristics of APAP assays cleared by the Food and Drug Administration’s (FDA) 510(k) premarket notification process by searching the Clinical Laboratory Improvement Amendments (CLIA) database. We collected the following data where available: test principle, precision near 10 mg/L, precision near 150 mg/L, limits of detection, and limits of quantitation.

Results

For all assays, absolute analytical precision decreased as analyte concentration increased. Near [APAP] = 10 mg/L, the most precise assays had a standard deviation (SD) of 0.2 mg/L or coefficient of variation (CV) of 1% and the least precise assays had a SD of 1.8 mg/L or a CV of 10%. Near [APAP] = 150 mg/L, the most precise assay had a SD of 1.4 mg/L or CV of 0.9% and the least precise assays had a SD of 7.4 mg/L or a CV of 4.9%.

Conclusions

Commercially available APAP assays had good analytical precision with improvement over time. The failure of some manufacturers to validate precision near treatment thresholds is concerning. Newer APAP assays can measure a wider range of [APAP], which likely improves the risk stratification of overdose patients but also carries a risk of overdiagnosis when minuscule quantities are detected.
Low-Cost Live Insect Scouting Drone: iDrone Bee
Authors: Ryu Jae Hyeon , Clements Justin , Neufeld Jerry
Published: July 2022

Unmanned aerial vehicles (UAVs, e.g., drones) are a common tool for many civil applications, including precision agriculture, transportation, delivery services, rescue missions, law enforcement, and more. Remote sensing technologies used in conjunction with drones are a dominant application in precision agriculture. Multispectral instrumentation attached to UAVs allows the user to observe multiple parameters, including the normalized difference vegetation index which can represent crop stresses induced by various factors (e.g., drought, insect outbreak, nutrient loss, and other diseases). However, little research has been done to apply drones to accomplish a mission-oriented actionable task in agriculture, such as insect sampling. We propose a low-cost, open source-based live insect scouting drone named ‘iDrone Bee’ to benefit the integrated pest management (IPM) community by minimizing time and efforts of human interventions while collecting live insects in agricultural fields. Herein we present instruction and operation procedures to build and operate an iDrone Bee for insect scouting in an agricultural ecosystem and validate the system in an alfalfa seed field. The findings of this investigation demonstrate that a drone-based insect scouting method may be a valuable tool to benefit the IPM community.
Assessing Urban Forest Threats across the Conterminous United States
Authors: Nowak David J , Greenfield Eric J , Ellis Alexis
Published: July 2022

Numerous threats to urban forests are assessed for the conterminous United States, including projected changes in urban tree cover, air temperatures, precipitation, aridity, sea level rise, wildfires, and flooding, as well as threats from hurricanes, tornadoes, ice storms, and insects and diseases. All potential threats were integrated into a cumulative threat index to illustrate which areas of the United States will likely face the greatest overall threat to their urban forests. Urban forests with the greatest cumulative threat per unit area are in the eastern United States, particularly in some coastal counties. Urban forests that have the greatest cumulative threat proportional to the percent of the county that is urbanized are in the highly urbanized areas along the DC–Boston corridor and in other metro areas (e.g., Atlanta, Georgia; Indianapolis, Indiana; Columbus, Ohio; Houston, Texas; Charlotte, North Carolina). By understanding local urban forest threats, management plans and policies can be enacted to help mitigate the impacts of and adapt to future threats to sustain healthy urban forests and associated benefits.

Study Implications: By understanding the magnitude and variation in potential urban forest threats, forest managers can be better prepared to potentially minimize and adapt to future urban forest damage. Threat type and intensities of threats vary by location. Understanding the distribution and intensity of urban forest threats can be used to help direct policies and forest management plans to sustain long-term urban forest health. A tool to assess urban forest threats by county is available in the supplemental materials.
A Mercantile Theory of Expert Knowledge Utilization in Patrimonialist Bureaucracies: Evidence from the Health Sector in Peru
Authors: Salazar-Morales Diego Alonso
Published: July 2022

This article formulates a theory of expert knowledge utilization in patrimonialist administrative traditions characterized by politicians’ predominance over bureaucrats. The argument is that in these weak institutional contexts acquiring “expert knowledge” enables politicians to control key bureaucratic functions that facilitates rent extraction to fund their campaigns, and in doing so, they eventually and circumstantially produce some positive welfare outcomes. My findings show that tenured politicians employ expert knowledge to expand their control over previously unknown administrative regulations, temporarily building capacities that enables them to (re)direct budgets to policy areas that report electoral gains, and sometimes incurring in collusion. In contrast, newcomer politicians often fail to take advantage of expert knowledge transferred given their inexperience in office hence producing less welfare outputs. This article sources evidence from a knowledge transfer program designed by the Peruvian central government to enlighten local politicians in the country’s fight against children stunting. Evidence combining a time-varying semiexperimental analysis (Panel DID) and in-depth interviews with regional and local politicians, as well as high level civil servants, largely confirm my theoretical claims.
Tumor size before image-guided brachytherapy is an important factor of local control after radiotherapy for cervical squamous cell carcinoma: analysis in cases using central shielding
Authors: Yoshio Kotaro , Ihara Hiroki , Okamoto Kazuhiro , Suzuki Etsuji , Ogata Takeshi , Sugiyama Soichi , Nakamura Keiichiro , Nagao Shoji , Masuyama Hisashi , Hiraki Takao
Published: July 2022

We analyzed the local control (LC) of cervical squamous cell carcinoma treated by computed tomography (CT)-based image-guided brachytherapy (IGBT) using central shielding (CS). We also examined the value of tumor diameter before brachytherapy (BT) as a factor of LC. In total, 97 patients were analyzed between April 2016 and March 2020. Whole-pelvic (WP) radiotherapy (RT) with CS was performed, and the total pelvic sidewall dose was 50 or 50.4 Gy; IGBT was delivered in 3–4 fractions. The total dose was calculated as the biologically equivalent dose in 2 Gy fractions, and distribution was modified manually by graphical optimization. The median follow-up period was 31.8 months (6.3–63.2 months). The 1- and 2-year LC rates were 89% and 87%, respectively. The hazard ratio was 10.11 (95% confidence interval: 1.48–68.99) for local recurrence in those with a horizontal tumor diameter ≥ 4 cm compared to those with < 4 cm before BT. In CT-based IGBT for squamous cell carcinoma, favorable LC can be obtained in patients with a tumor diameter < 4 cm before BT. However, if the tumor diameter is ≥ 4 cm, different treatment strategies such as employing interstitial-BT for dose escalation may be necessary.
Managing rare fractures – a case report of an isolated avulsion fracture of the peroneus longus tendon
Authors: Nand Raghav , Khan Muhammad Murtaza , Sunderamoorthy Dakshinamurthy
Published: July 2022

Avulsion fractures of the peroneus longus tendon are seldom seen and potentially can go undiagnosed during an emergency visit. If not managed appropriately, it can lead to chronic pain and suffering. This case report presents a 55-year-old postman who was seen in the clinic complaining of persistent pain over the instep of his right foot with no history of trauma. His pain was localized to the first metatarsophalangeal joint with some radiation to the heel. Magnetic resonance imaging revealed an isolated avulsion fracture of the first metatarsal, which was initially missed on X-ray. In this case, the patient was successfully treated with a mixture of steroid and local anesthetic injections. Following our intervention, the Manchester Oxford Foot Questionnaire was reduced from 33 to 0. The goal of this article is to raise awareness of this rare finding for doctors who may face this in accident and emergency (A&E), Orthopedic clinics or at a general practice (GP) practice.
How to write a systematic review or meta-analysis protocol
Authors: Al Shakarchi Julien
Published: July 2022

A protocol is an important document that specifies the research plan for a systematic review/meta analysis. In this paper, we have explained a simple and clear approach to writing a research study protocol for a systematic review or meta-analysis.
Reporting of Racial and Ethnic Minority Representation in Early Phase Pediatric Oncology Clinical Trials
Authors: Faruqi Aiman J , Ligon John A , Cohen Julia W , Akshintala Srivandana , Widemann Brigitte C , Shah Nirali N
Published: July 2022

This letter to the editor considers outcomes for underrepresented populations across early phase pediatric oncology clinical trials, considering barriers to equitable representation of minorities in clinical trials.
The plant TOR kinase tunes autophagy and meristem activity for nutrient stress-induced developmental plasticity
Authors: Dong Yihan , Aref Rasha , Forieri Ilaria , Schiel David , Leemhuis Wiebke , Meyer Christian , Hell Ruediger , Wirtz Markus
Published: July 2022

Plants, unlike animals, respond to environmental challenges with comprehensive developmental transitions that allow them to cope with these stresses. Here we discovered that antagonistic activation of the Target of Rapamycin (TOR) kinase in Arabidopsis thaliana roots and shoots is essential for the nutrient deprivation-induced increase in the root-to-shoot ratio to improve foraging for mineral ions. We demonstrate that sulfate limitation-induced downregulation of TOR in shoots activates autophagy, resulting in enhanced carbon allocation to the root. The allocation of carbon to the roots is facilitated by the specific upregulation of the sucrose-transporter genes SWEET11/12 in shoots. SWEET11/12 activation is indispensable for enabling sucrose to act as a carbon source for growth and as a signal for tuning root apical meristem activity via glucose-TOR signaling. The sugar-stimulated TOR activity in the root suppresses autophagy and maintains root apical meristem activity to support root growth to enhance mining for new sulfate resources in the soil. We provide direct evidence that the organ-specific regulation of autophagy is essential for the increased root-to-shoot ratio in response to sulfur limitation. These findings uncover how sulfur limitation controls the central sensor kinase TOR to enable nutrient recycling for stress-induced morphological adaptation of the plant body.
Effects of auditory sleep modulation approaches on brain oscillatory and cardiovascular dynamics
Authors: Huwiler Stephanie , Carro Dominguez Manuel , Huwyler Silja , Kiener Luca , Stich Fabia M , Sala Rossella , Aziri Florent , Trippel Anna , Schmied Christian , Huber Reto , Wenderoth Nicole , Lustenberger Caroline
Published: July 2022

Slow waves, the hallmark feature of deep nonrapid eye movement sleep, do potentially drive restorative effects of sleep on brain and body functions. Sleep modulation techniques to elucidate the functional role of slow waves thus have gained large interest. Auditory slow wave stimulation is a promising tool; however, directly comparing auditory stimulation approaches within a night and analyzing induced dynamic brain and cardiovascular effects are yet missing. Here, we tested various auditory stimulation approaches in a windowed, 10 s ON (stimulations) followed by 10 s OFF (no stimulations), within-night stimulation design and compared them to a SHAM control condition. We report the results of three studies and a total of 51 included nights and found a large and global increase in slow-wave activity (SWA) in the stimulation window compared to SHAM. Furthermore, slow-wave dynamics were most pronouncedly increased at the start of the stimulation and declined across the stimulation window. Beyond the changes in brain oscillations, we observed, for some conditions, a significant increase in the mean interval between two heartbeats within a stimulation window, indicating a slowing of the heart rate, and increased heart rate variability derived parasympathetic activity. Those cardiovascular changes were positively correlated with the change in SWA, and thus, our findings provide insight into the potential of auditory slow wave enhancement to modulate cardiovascular restorative conditions during sleep. However, future studies need to investigate whether the potentially increased restorative capacity through slow-wave enhancements translates into a more rested cardiovascular system on a subsequent day.
Expressive Writing for Korean Immigrant Older Adults Residing in Areas without Well-Established Korean Communities
Authors: Rhee Stephanie Lyu
Published: July 2022

This experimental study examined the effects of expressive writing (EW) and its differential effects by gender on acculturative stress and depressive symptoms among first-generation Korean immigrant older adults residing in areas without well-established Korean communities in the United States. A pretest–posttest control group design was used to assess a total of 25 participants at baseline, right after the final writing, and at one-month follow-up. Fifteen randomized experimental participants wrote about their stressful or traumatic experiences related to their immigration and acculturation, whereas 10 in the control group wrote about their daily routines for 15 to 20 minutes per day for three consecutive days. Mixed analyses of variance showed that participants in both writing conditions reported more acculturative stress and depressive symptoms right after the final writing. A two-way multivariate analysis of variance showed that the experimental group and female participants reported significantly fewer depressive symptoms at one-month follow-up relative to the control group and male participants; however, the same significant effect was not observed in acculturative stress. No significant interaction effect between writing conditions and gender was found on either of the outcome variables. EW can be a culturally sensitive and feasible short-term intervention for depressive symptoms among Korean immigrant older adults residing in areas lacking ethnic resources and services.
Implementing laboratory quality management in Africa and central Asia: a model for healthcare improvement
Authors: Mateta Patrick , Procop Gary W , Mtotela Wilson , Nyakuwocha Raymond , Fine Glen
Published: July 2022

Background

Optimized laboratory services are recognized as an integral part of high-quality healthcare delivery. However, these services are often unavailable or substandard in resource-limited countries. The implementation of quality management systems (QMSs) in the laboratory can transform laboratory services and ultimately improve patient care in these settings.

Methods

The Clinical and Laboratory Standards Institute, through its Global Health Partnerships (GHP) program, has intervened in 32 laboratories to implement QMSs and improve performance. Standardized checklists were used before and after the structured intervention to quantify the impact of this program.

Results

QMS implementation resulted in a statistically significant improvement in overall mean checklist scores. All participating laboratories demonstrated improvement in their quality and performance, with 13 laboratories achieving national accreditation within the time frame of this study.

Conclusion

A structured program that utilizes well-recognized, standardized checklists and has leadership and laboratory team support, professional training with onsite guidance (i.e. train the trainer) and access to professionals experienced with QMS implementation and maintenance can lead to significant improvements in quality in resource-limited countries.
Discovery and Evolution of Six Positive-Sense RNA Viruses Co-infecting the Hypovirulent Strain SCH733 of Sclerotinia sclerotiorum
Authors: Hai Du , Li Jincang , Lan Shangsong , Wu Tun , Li Ying , Cheng Jiasen , Fu Yanping , Lin Yang , Jiang Daohong , Wang Minghong , Xie Jiatao
Published: July 2022

Sclerotinia sclerotiorum is a well-known phytopathogenic fungus with a wide host range. Identifying novel mycoviruses in phytopathogenic fungi is necessary to develop novel strategies for plant health protection and contribute to understanding the origin of viruses. Six new mycoviruses with positive single-stranded RNA genomes co-infecting the hypovirulent strain SCH733 of S. sclerotiorum were identified using a metatranscriptomic approach, and their complete genome sequences were molecularly determined. These mycoviruses belong to the following five families: Narnaviridae, Mitoviridae, Deltaflexviridae, Botourmiaviridae, and Ambiguiviridae. Three of these mycoviruses belong to existing International Committee on Taxonomy of Viruses (ICTV)-recognized species. Two of these newly identified mycoviruses have unique genomic features that are significantly different from those of all known mycoviruses. Phylogenetic analysis revealed that these six mycoviruses included close as well as distant relatives of known mycoviruses, thereby providing new insight into virus evolution and classification. Mycovirus horizontal transmission and elimination experiments revealed that Sclerotinia sclerotiorum narnavirus 5 is associated with hypovirulence of S. sclerotiorum, although we have not shown that it is independently responsible for the hypovirulence phenotype. This study broadens the diversity of known mycoviruses infecting S. sclerotiorum and provides a clue toward limiting hypovirulence in S. sclerotiorum.
Gender Distribution of Authors of Evaluation Letters for Promotion at One Medical School
Authors: Logeais Mary E. , Eckerstorfer Margaret , Krohn Kristina M. , Everson-Rose Susan A. , Termuhlen Amanda M. , Joseph Anne M.
Published: July 2022

Purpose

Women remain underrepresented in key leadership positions and advanced ranks in academic medicine. This study examines the numbers of men and women letter writers for promotion candidates during a 5-year period across departments, tracks, ranks, and candidate gender.

Method

A descriptive study characterized the gender of evaluation letter writers for candidates for promotion to associate or full professor at the University of Minnesota Medical School between 2015 and 2020. Letter writer and candidate gender were characterized by self-identified pronouns in the faculty biography or dossier. Letter writer gender was described by candidate department, promotion track, rank, terminal degree, and gender.

Results

Among 299 candidates for promotion, 172 (58%) were men and 127 (42%) were women; dossiers included 3,995 evaluation letters. Across all years, men wrote more letters than women (external letters, range, 69% in 2019–2020 to 75% in 2015–2016; internal letters, range, 67% in 2018–2019 to 77% in 2015–2016). Candidates in the family medicine and pediatrics departments had the highest percentages of letters written by women (44% and 40%, respectively). No differences were found in the number of women letter writers by candidate promotion track; however, differences were found by candidate rank (associate professor, 30%; full professor, 23%) and terminal degree (MD/DO, 25%; PhD, 33%; MD–PhD, 20%). Regardless of candidate gender, most evaluation letters were written by men. Women candidates had 15% to 20% more letters authored by women than men candidates (34%–40% vs 18%–23%).

Conclusions

The gender pattern of letter writers may reflect implicit biases regarding gender and perceived leadership status, expertise, and success. Adopting policies that promote or require gender diversity among letter writers for promotion candidates may provide an opportunity to encourage faculty to seek diverse networks and recognize the achievements of women faculty.
Predictive Scoring for Recurrent Patellar Instability After a First-time Patellar Dislocation
Authors: Tan Si Heng Sharon , Chua Kasia Chen Xi , Yeo Lincoln Kai Pheng , Liang Shen , Lim Andrew Kean Seng , Hui James Hoipo
Published: July 2022

Purpose:

Patellofemoral instability is a common acute knee injury seen in the pediatric population. First-time patellar dislocations usually undergo conservative management, but ~15% to 80% of patients experience recurrent instability. This study aims to develop a prediction model using radiographic parameters of the patellofemoral joint seen on computed tomography scans in different degrees of knee flexion, to determine the risk of recurrence after the first episode of patellofemoral instability.

Methods:

A 12-year retrospective case-control study was performed. All patients in a single institution aged 18 years or younger who had a computed tomography patellar tracking scan performed for patellar instability were included. Predictors included in the score were determined through backward logistic regression and compared using receiver operating characteristic curve analysis.

Results:

This study revealed that recurrent dislocation in first-time patellofemoral dislocation could be accurately predicted using the prediction score that consisted of age, tibial tubercle-trochlear groove distance and congruence angle at 10- and 20-degree flexion. The sensitivity of the score was 100% and specificity was 73.3%. Three diagnostic zones were identified and used to categorize patients into low-, intermediate-, and high-probability groups.

Conclusion:

This study presented a scoring system that incorporated radiographic knee kinematics in the risk assessment for recurrent patellofemoral instability for patient stratification. The scoring system could guide the decision for early surgical intervention after the first-episode patellofemoral dislocation for patients at high risk of recurrent patellofemoral dislocation.
Comprehensive view on genetic features, therapeutic modalities and prognostic models in adult T-cell lymphoblastic lymphoma
Authors: Zou Qihua , Ma Shuyun , Tian Xiaopeng , Cai Qingqing
Published: July 2022

Adult T-cell lymphoblastic lymphoma (T-LBL) is a rare and aggressive subtype of non-Hodgkin’s lymphoma that differs from pediatric T-LBL and has a worse prognosis. Due to its rarity, little is known about the genetic and molecular characteristics, optimal treatment modalities, and prognostic factors of adult T-LBL. Therefore, we summarized the existing studies to comprehensively discuss the above issues in this review. Genetic mutations of NOTCH1/FBXW7, PTEN, RAS, and KMT2D, together with abnormal activation of signaling pathways, such as the JAK-STAT signaling pathway were described. We also discussed the therapeutic modalities. Once diagnosed, adult T-LBL patients should receive intensive or pediatric acute lymphoblastic leukemia regimen and central nervous system prophylaxis as soon as possible, and cranial radiation-free protocols are appropriate. Mediastinal radiotherapy improves clinical outcomes, but adverse events are of concern. Hematopoietic stem cell transplantation may be considered for adult T-LBL patients with high-risk factors or those with relapsed/refractory disease. Besides, several novel prognostic models have been constructed, such as the 5-miRNAs-based classifier, 11-gene-based classifier, and 4-CpG-based classifier, which have presented significant prognostic value in adult T-LBL.
Assessment of humoral immunity and nutritionally essential trace elements in steady-state sickle cell disease Nigerian children before and after Prevenar 13 pneumococcal vaccination
Authors: Arinola Ganiyu Olatunbosun , Disu Elizabeth , Babatunde Adedokun , Olopade Christopher , Olopade Olufunmilayo
Published: July 2022

Background:

Children with sickle cell disease (SCD) are particularly prone to pneumococcal infection and administration of Prevenar 13 pneumococcal vaccine in Nigerian children with SCD is yet to be wide spread. This call for the need to study humoral immune responses stimulated by Prevenar 13 pneumococcal vaccine in SCD children to confirm the benefit or otherwise for the use of Prevenar 13 pneumococcal vaccine.

Method:

The levels of humoral (innate and adaptive) immune factors and associated nutritionally essential trace elements were determined following Prevenar 13 pneumococcal vaccination of 23 Nigerian children with SCD. Serum innate humoral immune factors [Complement factors (C1q and C4), transferrin, ferritin, and C-reactive protein (CRP)] and adaptive humoral immune factors [IgG, IgA, IgM, and IgE] were determined using ELISA. Nutritionally essential trace elements such as iron (Fe), copper (Cu), and zinc (Zn) were measured also using an atomic absorption spectrophotometer.

Results:

The serum levels of certain innate humoral immune factors (ferritin, CRP, and C4), only one adaptive humoral immune factors (IgE), and essential trace elements (Fe, Zn, and Cu) were significantly elevated in children with SCD post Prevenar 13 pneumococcal vaccination when compared to prevaccination levels.

Conclusion:

Vaccination of children with SCD with Prevenar 13 pneumococcal vaccine was associated with increased levels of more innate humoral immune factors than adaptive factors. This study thus supports the administration of Prevenar 13 pneumococcal vaccination to children with SCD.
Addressing Futility: A Practical Approach
Authors: Kopar Piroska K. , Visani Adrienne , Squirrell Kyler , Brown Douglas E.
Published: July 2022

OBJECTIVES:

Limiting or withdrawing nonbeneficial medical care is considered ethically responsible throughout most of critical care and medical ethics literature. Practically, however, setting limits to treatment is often challenging. We review the literature to identify best practices for using the definition of futility as an anchoring concept to aid the ethical practice of ICU clinicians.

DATA SOURCES:

Source data were obtained from a PubMed literature review.

STUDY SELECTION:

English language articles were chosen based on relevance to medical futility ethics, end-of-life care in the ICU, or communication and conflict mitigation strategies.

DATA EXTRACTION:

Independent evaluation of selected articles for recurrent content themes as relevant to our clinical case were compared among authors and based on consensus, quantitative and qualitative data from these sources were referenced directly.

DATA SYNTHESIS:

When life-sustaining treatment is unlikely to achieve a meaningful benefit such as symptom improvement, continued care may be discordant with the patient’s goals. Institutional and cultural norms, unconscious biases, and difficulty with navigating conflicts all influence how un(comfortable) clinicians feel in setting limits to futile care. Defining futility in light of the patient’s goals and values, focusing on outcomes rather than interventions, and being proactive in communication with families are the staples of medically meaningful critical care. Palliative measures should be framed affirmatively, and clinicians should be transparent about the limits of medicine.

CONCLUSIONS:

Clinicians have an ethical obligation not to provide futile care. To practice accordingly, we must clearly understand the nature and forms of futility. Armed with this understanding, our discussions with family and surrogates in the ICU should fundamentally comprise 1) eliciting the patient’s values and goals, 2) communicating which interventions serve those values and goals and which do not, and 3) offering only those interventions whose likely outcomes are in line with said values and goals.
Training to Enhance the Knowledge and Comfort Level of Emergency Physicians Providing Care for Survivors of Sexual Assault
Authors: Prusky Melissa A. , Solomon Chloe J. E. , Tracy Kaitlynn P. , Shah Shital C. , Rodriguez Jaclyn , Balata Maria , York Sloane L. , Rumoro Dino P.
Published: July 2022

Introduction:

Although sexual assault (SA) is a substantial public health problem, emergency physicians do not universally undergo continuing education on caring for survivors of SA. The goal of this intervention was to develop a training course that improves physician understanding of trauma-sensitive care in the emergency department and equips physicians with knowledge of the specialized care required to treat SA survivors.

Methods:

Thirty-nine attending emergency physicians underwent a 4-hour training on trauma-sensitive care for survivors of SA and completed prequestionnaires and postquestionnaires to assess training efficacy in improving knowledge base and comfort level providing care. The training consisted of didactic portions focused on the neurobiology of trauma, communication skills, and forensic evidence collection techniques and a simulation portion with standardized patients to practice evidence collection and a trauma-sensitive anogenital examination.

Results:

Physicians demonstrated significantly improved performance (P < .05) on 12 of 18 knowledge-based questions. Physicians also showed significant improvement (P < .001) on 11 of 11 Likert scale questions that assessed comfort level communicating with survivors and using trauma-sensitive techniques during medical and forensic examinations.

Conclusion:

Physicians who received the training course demonstrated a significantly improved knowledge base and comfort level treating survivors of SA. Considering the prevalence of sexual violence, it is imperative that physicians are appropriately educated on trauma-sensitive care.
Family Physician Quality Improvement Plans: A Realist Inquiry Into What Works, for Whom, Under What Circumstances
Authors: Roy Marguerite , Lockyer Jocelyn , Touchie Claire
Published: July 2022

Introduction:

Evaluation of quality improvement programs shows variable impact on physician performance often neglecting to examine how implementation varies across contexts and mechanisms that affect uptake. Realist evaluation enables the generation, refinement, and testing theories of change by unpacking what works for whom under what circumstances and why. This study used realist methods to explore relationships between outcomes, mechanisms (resources and reasoning), and context factors of a national multisource feedback (MSF) program.

Methods:

Linked data for 50 physicians were examined to determine relationships between action plan completion status (outcomes), MSF ratings, MSF comments and prescribing data (resource mechanisms), a report summarizing the conversation between a facilitator and physician (reasoning mechanism), and practice risk factors (context). Working backward from outcomes enabled exploration of similarities and differences in mechanisms and context.

Results:

The derived model showed that the completion status of plans was influenced by interaction of resource and reasoning mechanisms with context mediating the relationships. Two patterns were emerged. Physicians who implemented all their plans within six months received feedback with consistent messaging, reviewed data ahead of facilitation, coconstructed plan(s) with the facilitator, and had fewer risks to competence (dyscompetence). Physicians who were unable to implement any plans had data with fewer repeated messages and did not incorporate these into plans, had difficult plans, or needed to involve others and were physician-led, and were at higher risk for dyscompetence.

Discussion:

Evaluation of quality improvement initiatives should examine program outcomes taking into consideration the interplay of resources, reasoning, and risk factors for dyscompetence.