bluuebunny/crossref_metadata_2025 huggingface dataset:
Mental Health and Older Adults
Authors: Lee Hee Yun , Hasenbein William , Gibson Priscilla
Published: August 2020

As the older adult population continues to grow at a rapid rate, with an estimated 2.1 billion older adults in 2050, social welfare researchers are determined to fill the shortage of gerontological social workers and structural lag to best serve the baby boomers who are expected to need different services than previous generations. Mental illness impacts over 20% of older adults in the world and the United States. The major mental health issues in older adults include depression, anxiety, loneliness, and social isolation. Depression is considered one of the most common mental health issues among this population; however, the prevalence could be underestimated due to older adults linking relevant symptoms to other causes, such as old age, instead of as possible depression. Like depression, anxiety symptoms are often mistaken as results of aging. It is also difficult for providers to diagnose anxiety in this population due to anxiety frequently being coupled with other illnesses and the psychological stress that comes with old age. Because the presence of loneliness or social isolation can manifest depression and anxiety symptoms in older adults, it is also difficult to separate these two issues. With the anticipated increase of the older adult population within the next few years, measurement tools have been created to assess depression and anxiety specifically for older adults. In addition to adapting assessment tools, interventions tailored to older adults are essential to ensure treatment coherence, even though medications are the go-to treatment option.
Lieberman, Florence
Authors: Logan Sadye L. M.
Published: August 2020

Florence Lieberman (1918–2011) made extraordinary contributions to the field of clinical social work in New York City while a professor at Hunter College School of Social Work (now Silberman School of Social Work), where she served from 1966 to 1986.
Coronavirus Disease 2019 (COVID-19) Response in Zimbabwe: A Call for Urgent Scale-up of Testing to meet National Capacity
Authors: Dzinamarira Tafadzwa , Mukwenha Solomon , Eghtessadi Rouzeh , Cuadros Diego F , Mhlanga Gibson , Musuka Godfrey
Published: August 2020

Control of coronavirus disease 2019 (COVID-19) heavily relies on universal access to testing in order to identify who is infected; track them to make sure they do not spread the disease further; and trace those with whom they have been in contact. The recent surge in COVID-19 cases in Zimbabwe is an urgent national public health concern and requires coordinated efforts to scale up testing using the capacity already in existence in the country. There is a need for substantial decentralization of testing, investment in better working conditions for frontline health workers, and the implementation of measures to curb corruption within government structures.
Coverage rates against vaccine-preventable diseases among healthcare workers in Sicily (Italy)
Authors: Ledda Caterina , Rapisarda Venerando , Maltezou Helena C , Contrino Eleonora , Conforto Arianna , Maida Carmelo Massimo , Tramuto Fabio , Vitale Francesco , Costantino Claudio
Published: August 2020

Background

Vaccination of healthcare workers (HCWs) reduces the risk of occupational vaccine-preventable diseases (VPDs), prevents their nosocomial transmission and preserves healthcare delivery during outbreaks. Extensive implementation of vaccination programmes for HCWs allowed the elimination or control of several VPDs within healthcare facilities; despite these, the vaccine adherence rates among HCWs are persistently suboptimal.

Methods

A questionnaire was self-administered by HCWs to assess their vaccination rates against several VPDs and self-reported immunity in two university hospitals of Southern Italy (Catania and Palermo).

Results

A total of 2586 questionnaires were analysed. More than 50% of HCWs did not know their own immunization status against diphtheria, tetanus and pertussis. More than half of the HCWs interviewed at University Hospital (UH) of Catania (UHC) was immune against measles (72.1%), in contrast with data reported at the UH of Palermo (UHP) (45.9%). Immunization status against mumps (67.5% UHC vs. 40.6% UHP), rubella (69.9% UHC vs. 46.6% UHP) and varicella (70.4% UHC vs. 50.7% UHP). Overall, about 30% of HCWs did not know their own immunization status against these VPDs. Moreover, 84.2% at UHC and 66.7% at UHP stated that was previously vaccinated against hepatitis B.

Conclusion

Vaccination coverage rates reported from the HCWs against influenza during the last three seasons were considerably low. In conclusion, totally inadequate vaccination rates against several VPDs were found in two university hospitals in Sicily, in terms of preventing not only disease transmission by susceptible HCWs, but also nosocomial outbreaks, confirming data from previous national and international studies.
Health literacy and adherence to treatment in different districts in Chile
Authors: Durán Doris , Retamal Ignacio , Ochoa Tatiana , Monsalves Maria Jose
Published: August 2020

The relationship between health literacy and adherence has been described in medical literature, especially for patients with non-communicable diseases (NCDs). However, the relevance that an individual’s local context can have has not been considered. This study aimed to examine the association of both concepts at a population level and estimate the correlation between health literacy and adherence to pharmacological treatment in adults from 14 districts in different regions in Chile. A cross-sectional study was carried out in 14 districts from 3 different regions of Chile. Sampling was carried out by volunteers. Three questionnaires were applied: sociodemographic; Morisky-Green-Levine (MMAS-4) and the Short Assessment of Health Literacy for Spanish Adults test (SAHLSA-50). Data were analyzed descriptively, and a Multilevel Poisson Regression model was fitted to evaluate the relationship between health literacy and adherence to pharmacological treatment, considering the districts as fixed intercepts. A total of 1,336 persons were surveyed; 811 self-reported as having at least 1 NCD. A 83.4% had adequate literacy and 37.1% were adherent to pharmacological treatment, regardless of their health literacy. A 3.6% (variance partition coefficient = 0.036) correlation of adherence to treatment was observed in respondents living in the same district. Those with inadequate health literacy had a 12% greater prevalence of being non-adherent (prevalence ratio 1.12; IC 95% 0.87 − 1.47) when adjusting for individual variables. These results could suggest that the individual’s local context does not influence the relation of functional health literacy and adherence to pharmacological treatment in populations with basic and intermediate levels of education. We suggest further studies in this matter.
On the W 2
p Estimate for Oblique Derivative Problem in Lipschitz Domains
Authors: Dong Hongjie , Li Zongyuan
Published: August 2020

The aim of this paper is to establish $W^2_p$ estimate for non-divergence form 2nd-order elliptic equations with the oblique derivative boundary condition in domains with small Lipschitz constants. Our result generalizes those in [ 16] and [ 17], which work for $C^{1,\alpha }$ domains with $\alpha> 1-1/p$. As an application, we also obtain a solvability result. An extension to fully nonlinear elliptic equations with the oblique derivative boundary condition is also discussed.
Ideal conditions for increased trapping success of pygmy rabbits (Brachylagus idahoensis) across the Great Basin
Authors: Crowell M M , Shoemaker K T , Matocq M D
Published: August 2020

Sagebrush-steppe ecosystems are one of the most imperiled ecosystems in North America and many of the species that rely on these habitats are of great conservation concern. Pygmy rabbits (Brachylagus idahoensis) are one of these species. They rely on sagebrush year-round for food and cover, and are understudied across their range in the intermountain west due in part to their recalcitrance to standard capture techniques. Identifying an efficient and minimally biased trapping method therefore is a critical first step in learning more about this species. We assessed how trap orientation and weather characteristics influenced trap success for Tomahawk traps placed in and around pygmy rabbit burrows by carrying out trapping surveys at 16 occupied pygmy rabbit sites across the Great Basin from 2016 to 2018. We found that pygmy rabbits had a greater probability of being captured in traps with the open end facing away from burrow entrances. Pygmy rabbits also were more likely to be captured on clear days (0–5% cloud cover) and during periods of cooler temperatures during summer months (June–August). We found no evidence that sex or age ratios differed, or that individuals differed meaningfully, in their preference for certain trap orientations. To increase trap success for pygmy rabbits, we suggest maximizing trapping effort during summer months, at dawn, and maximizing the proportion of Tomahawk traps facing away from burrow entrances. We anticipate that our monitoring protocol will enable more effective research into the ecology and conservation of this cryptic and potentially imperiled species.
Phaeochromocytoma recurrence in a patient with multiple endocrine neoplasia type 2A
Authors: Gupta Rishabh
Published: August 2020

Multiple endocrine neoplasia type 2A (MEN2A) is a hereditary syndrome associated with tumours of the endocrine system. Principally, it is characterized by medullary thyroid carcinoma (MTC) with some individuals also developing phaeochromocytoma and hyperparathyroidism. Patients with fewer than two clinical features require either an identification of a germline rearranged in transfection mutation, or MEN2A characteristics in first-degree relatives, to establish a diagnosis of MEN2A. We present the case of a 54-year-old female with MEN2A, diagnosed by genetic screening, due to a substantial history of the disease in her ancestry. This case outlines the successful treatment of recurrent phaeochromocytoma, through the medium of radioactive iobenguane as an adjunct to surgical management. The report focuses particularly on the significance of innovative treatment strategies and forthcoming approaches to improve patient care in treating phaeochromocytoma in MEN2A.
Beneficial rhizobacteria Pseudomonas simiae WCS417 induce major transcriptional changes in plant sugar transport
Authors: Desrut Antoine , Moumen Bouziane , Thibault Florence , Le Hir Rozenn , Coutos-Thévenot Pierre , Vriet Cécile
Published: August 2020

Plants live in close relationships with complex populations of microorganisms, including rhizobacterial species commonly referred to as plant growth-promoting rhizobacteria (PGPR). PGPR are able to improve plant productivity, but the molecular mechanisms involved in this process remain largely unknown. Using an in vitro experimental system, the model plant Arabidopsis thaliana, and the well-characterized PGPR strain Pseudomonas simiae WCS417r (PsWCS417r), we carried out a comprehensive set of phenotypic and gene expression analyses. Our results show that PsWCS417r induces major transcriptional changes in sugar transport and in other key biological processes linked to plant growth, development, and defense. Notably, we identified a set of 13 genes of the SWEET and ERD6-like sugar transporter gene families whose expression is up- or down-regulated in response to seedling root inoculation with the PGPR or exposure to their volatile compounds. Using a reverse genetic approach, we demonstrate that SWEET11 and SWEET12 are functionally involved in the interaction and its plant growth-promoting effects, possibly by controlling the amount of sugar transported from the shoot to the root and to the PGPR. Altogether, our study reveals that PGPR-induced beneficial effects on plant growth and development are associated with changes in plant sugar transport.
Soybean TILLING-by-Sequencing+ reveals the role of novel GmSACPD members in unsaturated fatty acid biosynthesis while maintaining healthy nodules
Authors: Lakhssassi Naoufal , Zhou Zhou , Liu Shiming , Piya Sarbottam , Cullen Mallory A , El Baze Abdelhalim , Knizia Dounya , Patil Gunvant B , Badad Oussama , Embaby Mohamed G , Meksem Jonas , Lakhssassi Aicha , AbuGhazaleh Amer , Hewezi Tarek , Meksem Khalid
Published: August 2020

Developing soybean lines with high levels of stearic acid is a primary goal of the soybean industry. Most high-stearic-acid soybeans carry different GmSACPD-C mutated alleles. However, due to the dual role of GmSACPD-C in seeds and nodule development, all derived deleterious GmSACPD-C mutant alleles are of extremely poor agronomic value because of defective nodulation. The soybean stearoyl-acyl carrier protein desaturase (GmSACPD) gene family is composed of five members. Comparative genomics analysis indicated that SACPD genes were duplicated and derived from a common ancestor that is still present in chlorophytic algae. Synteny analysis showed the presence of segment duplications between GmSACPD-A/GmSACPD-B, and GmSACPD-C/GmSACPD-D. GmSACPD-E was not contained in any duplicated segment and may be the result of tandem duplication. We developed a TILLING by Target Capture Sequencing (Tilling-by-Sequencing+) technology, a versatile extension of the conventional TILLING by sequencing, and successfully identified 12, 14, and 18 ethyl methanesulfonate mutants at the GmSACPD-A, GmSACPD-B, and GmSACPD-D genes, respectively. Functional analysis of all identified mutants revealed an unprecedented role of GmSACPD-A, GmSACPD-B, and GmSACPD-D in unsaturated fatty acid biosynthesis without affecting nodule development and structure. This discovery will positively impact the development of high-stearic-acid lines to enhance soybean nutritional value without potential developmental tradeoffs.
The Development and Implementation of Specimens for Accident Forensic Toxicology Investigation Kit for Special Operations Forces
Authors: Caldara Gabrielle N , Isbester Michelle , Sartori David , Wilson Ramey L
Published: August 2020

Introduction

After a vehicle rollover led to the death of a military member in Central Africa in 2018, it became apparent there was a significant gap in the capability to collect toxicology samples of Service Members involved in accidents and mishaps at remote Special Operations Forces locations in Africa. Multiple misconceptions surrounding sample collection, procedures for laboratory evaluation, and methods for shipment signaled the importance of establishing a procedure and a plan to provide the necessary medical inventory to properly collect and ship samples.

Materials and Methods

The Special Operations Command Africa (SOCAFRICA) Surgeon’s Office gathered the appropriate supplies for collection of forensic toxicology samples, and simultaneously developed a step-by-step checklist to safely and correctly perform urine and blood collection. The procedures were further improved after the completion of cognitive interviews with a Navy corpsman and Army Civil Affairs medic. Multiple shipping iterations occurred to ensure safe movement and arrival of samples at Armed Forces Medical Examiner System Dover AFB. Two Separate Specimens for Accident Forensic Toxicology Investigation Kits were generated to accommodate personnel typically associated with accidents involving vehicles and aircraft.

Results

SOCAFRICA’s toxicology kit supports legal and medical chain of custody requirements for investigations, and provides deployed forces in Africa with a mechanism to collect and ship samples from Africa to Dover AFB. The kits are provided to ensure these samples are successfully analyzed, thereby removing any ambiguity surrounding an accident or mishap.

Conclusion

SOCAFRICA established a prepared kit with all of the materials for sample collection, accompanied by step-by-step descriptions of the procedure, and clear guidance on the proper completion of the requisite paperwork that meets medico-legal requirements.
Formation of the large nearby galaxies
Authors: Peebles P J E
Published: August 2020

Simulations of galaxy formation tend to place star particles in orbits seriously different from circular in numbers far larger than seem reasonable for the bulges and stellar haloes of the nearby L ∼ L* galaxies that can be examined in particularly close detail. I offer an example of how the situation might be improved: a prescription for non-Gaussian initial conditions on the scale of galaxies.
Exploring Protein Space: From Hydrolase to Ligase by Substitution
Authors: Hecht Nir , Monteil Caroline L , Perrière Guy , Vishkautzan Marina , Gur Eyal
Published: August 2020

The understanding of how proteins evolve to perform novel functions has long been sought by biologists. In this regard, two homologous bacterial enzymes, PafA and Dop, pose an insightful case study, as both rely on similar mechanistic properties, yet catalyze different reactions. PafA conjugates a small protein tag to target proteins, whereas Dop removes the tag by hydrolysis. Given that both enzymes present a similar fold and high sequence similarity, we sought to identify the differences in the amino acid sequence and folding responsible for each distinct activity. We tackled this question using analysis of sequence–function relationships, and identified a set of uniquely conserved residues in each enzyme. Reciprocal mutagenesis of the hydrolase, Dop, completely abolished the native activity, at the same time yielding a catalytically active ligase. Based on the available Dop and PafA crystal structures, this change of activity required a conformational change of a critical loop at the vicinity of the active site. We identified the conserved positions essential for stabilization of the alternative loop conformation, and tracked alternative mutational pathways that lead to a change in activity. Remarkably, all these pathways were combined in the evolution of PafA and Dop, despite their redundant effect on activity. Overall, we identified the residues and structural elements in PafA and Dop responsible for their activity differences. This analysis delineated, in molecular terms, the changes required for the emergence of a new catalytic function from a preexisting one.
Recent advances in the nucleolar responses to DNA double-strand breaks
Authors: Korsholm Lea Milling , Gál Zita , Nieto Blanca , Quevedo Oliver , Boukoura Stavroula , Lund Casper Carstens , Larsen Dorthe Helena
Published: August 2020

DNA damage poses a serious threat to human health and cells therefore continuously monitor and repair DNA lesions across the genome. Ribosomal DNA is a genomic domain that represents a particular challenge due to repetitive sequences, high transcriptional activity and its localization in the nucleolus, where the accessibility of DNA repair factors is limited. Recent discoveries have significantly extended our understanding of how cells respond to DNA double-strand breaks (DSBs) in the nucleolus, and new kinases and multiple down-stream targets have been identified. Restructuring of the nucleolus can occur as a consequence of DSBs and new data point to an active regulation of this process, challenging previous views. Furthermore, new insights into coordination of cell cycle phases and ribosomal DNA repair argue against existing concepts. In addition, the importance of nucleolar-DNA damage response (n-DDR) mechanisms for maintenance of genome stability and the potential of such factors as anti-cancer targets is becoming apparent. This review will provide a detailed discussion of recent findings and their implications for our understanding of the n-DDR. The n-DDR shares features with the DNA damage response (DDR) elsewhere in the genome but is also emerging as an independent response unique to ribosomal DNA and the nucleolus.
Women and Conflict Studies
Authors: Best Rebecca
Published: August 2020

Traditionally, women have been viewed as having little agency in wars and conflicts. Women were thought neither to cause the wars nor to fight them. When women were considered at all by scholars of war, they were conceived of primarily as victims. As women gained the franchise and ultimately began to be elected into political office in advanced democracies, some scholars began to consider the foreign policy implications of this—that is, do women’s attitudes toward war and defense policy differ from those of men and do these views produce different outcomes at the ballot box? Furthermore, do women behave differently with regard to security issues once in national office? Does their presence change the way their male colleagues vote on these issues? In recent decades, scholarship emerging first from critical feminist theory and later from positivist political scientists has begun to look more explicitly for women’s roles, experiences, and influences on and in conflict. This work has led to the recognition that, even when victimized in war, women have agency, and to the parallel conclusion that men’s agency is not as complete as scholars, practitioners, and the public have often assumed. This bibliography provides an overview of the development of women and conflict literature as well as several prominent themes and questions within the literature. It is of necessity incomplete and interested scholars are encouraged to review related articles in Oxford Bibliographies in International Relations, such as “Feminist Security Studies” by Kristen P. Williams, and “Women and Peacemaking/Peacekeeping” by Sabrina Karim and Kyle Beardsley.
Stanford Prison Experiment (SPE): Icon and Controversy
Authors: Devonis David C.
Published: August 2020

The Stanford Prison Experiment (SPE) took place at a time when the sources of authoritarianism and evil were a focal concern in psychology. It emerged from a tradition of activist social psychological research beginning with Solomon Asch in the 1940s and extending through Stanley Milgram’s obedience experiments in the early 1960s. The SPE was a product of the research program of social psychologist Philip Zimbardo, a member of the Stanford psychology faculty since 1968. Discussions among Zimbardo’s students in spring 1971 led to a plan to simulate a prison environment. They converted portions of the basement of a University building into a combination booking room and jail. Zimbardo and a number of his graduate and undergraduate students took on supervisory roles. Before the Experiment began, paid participants recruited through newspaper advertisements were screened to eliminate obvious psychopathology, then randomly assigned to either the role of ‘guard’ or ‘prisoner.’ On the first experimental morning August 14, 1971, actual local police simulated an arrest of each of the prisoner participants. After they arrived, blindfolded, a simulated booking took place. Guards escorted them to the prison hallway where prisoners were required to strip and exchange their clothing for simple shifts and slippers. After a simulated spray delousing, they entered makeshift cells. After this, the Experiment evolved as an extended improvisation, by both the guards and prisoners, on prison-related themes. Episodes of deprivation, bullying, and humiliation emerged unplanned. Originally planned to run for two weeks, the Experiment lasted only six days, prematurely terminated when its supervising personnel judged that the simulation had gotten out of their control. The coincidence of its termination with the Attica prison uprising in New York led to its immediate dissemination in the news. Since then the SPE has become one of the most iconic psychological studies of psychology’s modern era. Although intended to expose and ameliorate bad prison conditions, its effectiveness in this regard diminished during a rapid shift in US prison policy, in the mid-1970’s, from reform to repression. Over succeeding decades, the Experiment continued to stimulate the popular imagination, leading to an extensive replication on British television and its portrayal in two feature films. Soon after its original publication, the SPE attracted criticisms of its methodology. After 2010, critical scrutiny of the SPE as well as similar iconic studies from the 1960s and 1970s increased, fueled by the growing ‘replication crisis’ in psychology. This most recent phase of criticism reflects not just a turn toward reflexive disciplinary self-criticism but also the increased availability of archival sources for examination. The SPE continues to excite both passionate support and equally passionate obloquy, much as have other comparable simulations of human social behavior.
Grounded Theory
Authors: Lin Zhuo , Hollensbe Elaine
Published: August 2020

Grounded theory is a commonly used approach to analyzing qualitative data in management studies. It was originally developed by Barney Glaser and Anselm Strauss in the 1960s as a means of generating middle-range theories in sociology, and it has since moved across disciplines and developed in different versions (e.g., Glasserian, Straussian, constructivist grounded theory). Grounded theory seeks to construct theory that emerges from the data (i.e., theory “grounded” in data), and is characterized by an iterative process in which the researcher constantly compares the emerging theory, the data, and existing literature, engages in theoretical sampling, and strives for theoretical saturation of the data.
Epidemiologic and Microbiologic Characteristics of Hospitalized Patients Co-colonized With Multiple Species of Carbapenem-Resistant Enterobacteriaceae in the United States
Authors: Adediran Timileyin , Harris Anthony D , Johnson J Kristie , Calfee David P , Miller Loren G , Nguyen M Hong , Morgan Daniel J , Goodman Katherine E , Hitchcock Stephanie , Pineles Lisa , O’Hara Lyndsay M
Published: August 2020

We describe the epidemiologic and microbiologic characteristics of patients co-colonized with different species of carbapenem-resistant Enterobacteriaceae (CRE) from 5 hospitals in 4 states. Twenty-eight of 313 patients (8.9%) were co-colonized with at least 2 different CRE species. Different species within the same patient showed identical mechanism resistance in 18/28 (64%) cases.
Disseminated Nannizziopsis Infection in an Adolescent With a STAT1 Mutation
Authors: Most Zachary M , Lieu Tiffany , Filkins Laura , Nicolaides Rory , Rakheja Dinesh , Gelfand Andrew , Kahn Jeffrey
Published: August 2020

An adolescent with failure to thrive developed cuboid bone osteomyelitis and brain abscesses. Mold isolated from both locations was identified by universal genetic sequencing as Nannizziopsis spp, which is typically a pathogen of reptiles. The patient was subsequently diagnosed with a STAT1 mutation and was successfully treated.
Quantum-corrected thermodynamics and P–V criticality of self-gravitating Skyrmion black holes
Authors: Khan Yawar H , Ganai Prince A , Upadhyay Sudhaker
Published: August 2020

We study the quantum-corrected thermodynamics of a class of black holes generated by self-gravitating Skyrmion models. One such black hole solution is the Einstein–Skrymion black hole. We first compute the Arnowitt–Deser–Misner mass of an Einstein–Skyrmion black hole using an on-shell Hamiltonian formalism already present in the literature. We then consider nonextended phase space thermodynamics and derive expressions for various thermodynamic quantities like the Hawking temperature, entropy, pressure, Gibbs free energy, and heat capacity. Next, we study the effect of quantum corrections on the thermodynamics of the Einstein–Skyrmion black hole. We observe that apart from leading to stability, the quantum correction induces an anti-de Sitter to de Sitter phase transition in the Einstein–Skrymion black hole. Treating the cosmological constant as the pressure, we determine the $P$–$V$ criticality of the Einstein–Skrymion black hole and observe that it depends on the model parameters $\lambda$ and $K$. This study of the $P$–$V$ criticality could help to estimate the experimental bound on the values of $\lambda$ and $K$.
Arbitrage Portfolios
Authors: Kim Soohun , Korajczyk Robert A , Neuhierl Andreas
Published: August 2020

We propose a new methodology for forming arbitrage portfolios that utilizes the information contained in firm characteristics for both abnormal returns and factor loadings. The methodology gives maximal weight to risk-based interpretations of characteristics’ predictive power before any attribution is made to abnormal returns. We apply the methodology to simulated economies and to a large panel of U.S. stock returns. The methodology works well in our simulation and when applied to stocks. Empirically, we find the arbitrage portfolio has (statistically and economically) significant alphas relative to several popular asset pricing models and annualized Sharpe ratios ranging from 1.31 to 1.66.
A phase 2 randomized, double-blind, placebo-controlled, proof-of-concept study of oral seletalisib in primary Sjögren’s syndrome
Authors: Juarez Maria , Diaz Nieves , Johnston Geoffrey I , Nayar Saba , Payne Andrew , Helmer Eric , Cain Dionne , Williams Paulette , Devauchelle-Pensec Valerie , Fisher Benjamin A , Giacomelli Roberto , Gottenberg Jacques-Eric , Guggino Giuliana , Kvarnström Marika , Mariette Xavier , Ng Wan Fai , Rosas José , Sánchez Bursón Juan , Triolo Giovanni , Barone Francesca , Bowman Simon J
Published: August 2020

Objectives

This phase 2 proof-of-concept study (NCT02610543) assessed efficacy, safety and effects on salivary gland inflammation of seletalisib, a potent and selective PI3Kδ inhibitor, in patients with moderate-to-severe primary Sjögren’s syndrome (PSS).

Methods

Adults with PSS were randomized 1:1 to seletalisib 45 mg/day or placebo, in addition to current PSS therapy. Primary end points were safety and tolerability and change from baseline in EULAR Sjögren’s Syndrome Disease Activity Index (ESSDAI) score at week 12. Secondary end points included change from baseline at week 12 in EULAR Sjögren’s Syndrome Patient Reported Index (ESSPRI) score and histological features in salivary gland biopsies.

Results

Twenty-seven patients were randomized (seletalisib n = 13, placebo n = 14); 20 completed the study. Enrolment challenges led to early study termination with loss of statistical power (36% vs 80% planned). Nonetheless, a trend for improvement in ESSDAI and ESSPRI [difference vs placebo: –2.59 (95% CI: –7.30, 2.11; P=0.266) and –1.55 (95% CI: –3.39, 0.28), respectively] was observed at week 12. No significant changes were seen in saliva and tear flow. Serious adverse events (AEs) were reported in 3/13 of patients receiving seletalisib vs 1/14 for placebo and 5/13 vs 1/14 discontinued due to AEs, respectively. Serum IgM and IgG concentrations decreased in the seletalisib group vs placebo. Seletalisib demonstrated efficacy in reducing size and organisation of salivary gland inflammatory foci and in target engagement, thus reducing PI3K-mTOR signalling compared with placebo.

Conclusion

Despite enrolment challenges, seletalisib demonstrated a trend towards clinical improvement in patients with PSS. Histological analyses demonstrated encouraging effects of seletalisib on salivary gland inflammation and organisation.

Trial registration

https://clinicaltrials.gov, NCT02610543.
Large-Scale Evidence for an Association Between Peripheral Inflammation and White Matter Free Water in Schizophrenia and Healthy Individuals
Authors: Di Biase Maria A , Zalesky Andrew , Cetin-Karayumak Suheyla , Rathi Yogesh , Lv Jinglei , Boerrigter Danny , North Hayley , Tooney Paul , Pantelis Christos , Pasternak Ofer , Shannon Weickert Cynthia , Cropley Vanessa L
Published: August 2020

Introduction

Clarifying the role of neuroinflammation in schizophrenia is subject to its detection in the living brain. Free-water (FW) imaging is an in vivo diffusion-weighted magnetic resonance imaging (dMRI) technique that measures water molecules freely diffusing in the brain and is hypothesized to detect inflammatory processes. Here, we aimed to establish a link between peripheral markers of inflammation and FW in brain white matter.

Methods

All data were obtained from the Australian Schizophrenia Research Bank (ASRB) across 5 Australian states and territories. We first tested for the presence of peripheral cytokine deregulation in schizophrenia, using a large sample (N = 1143) comprising the ASRB. We next determined the extent to which individual variation in 8 circulating pro-/anti-inflammatory cytokines related to FW in brain white matter, imaged in a subset (n = 308) of patients and controls.

Results

Patients with schizophrenia showed reduced interleukin-2 (IL-2) (t = −3.56, P = .0004) and IL-12(p70) (t = −2.84, P = .005) and increased IL-6 (t = 3.56, P = .0004), IL-8 (t = 3.8, P = .0002), and TNFα (t = 4.30, P < .0001). Higher proinflammatory signaling of IL-6 (t = 3.4, P = .0007) and TNFα (t = 2.7, P = .0007) was associated with higher FW levels in white matter. The reciprocal increases in serum cytokines and FW were spatially widespread in patients encompassing most major fibers; conversely, in controls, the relationship was confined to the anterior corpus callosum and thalamic radiations. No relationships were observed with alternative dMRI measures, including the fractional anisotropy and tissue-related FA.

Conclusions

We report widespread deregulation of cytokines in schizophrenia and identify inflammation as a putative mechanism underlying increases in brain FW levels.
Taxonomy and molecular phylogeny of four karyorelictid species belonging to the genera Apotrachelocerca and Tracheloraphis (Protozoa: Ciliophora), with descriptions of two new species
Authors: Ma Mingzhen , Xu Yuan , Yan Ying , Li Yuqing , Warren Alan , Song Weibo
Published: August 2020

The taxonomy and phylogeny of four trachelocercid ciliates, Apotrachelocerca orientalis sp. nov., Tracheloraphis apoligostriata sp. nov., T. oligostriata and T. prenanti, isolated from marine habitats in Qingdao, China, were studied. The new species, A. orientalis sp. nov., can be distinguished from its most closely related congener, A. arenicola, by the absence of cortical granules and its conspicuously different SSU rDNA sequence. Tracheloraphis apoligostriata sp. nov. differs from the similar T. oligostriata by its body shape, distribution pattern of the cortical granules and SSU rDNA sequence. Based on available data, we suggest that T. prenanti can be defined by its colourless, globular cortical granules, which indicates that this species should be removed from the T. phoenicopterus-complex. Phylogenetic analyses based on SSU rDNA sequence data indicates that: A. orientalis sp. nov. groups with A. arenicola with full support, together sister to all other trachelocercid species; and T. cf. phoenicopterus, T. prenanti, T. oligostriata and T. apoligostriata sp. nov. form a clearly outlined clade.
Harnessing Pseudomonas protegens to Control Bacterial Panicle Blight of Rice
Authors: Ortega Laura , Walker Katherine A. , Patrick Casey , Wamishe Yeshi , Rojas Alejandro , Rojas Clemencia M.
Published: August 2020

Bacterial panicle blight of rice is a seedborne disease caused by the bacterium Burkholderia glumae. This disease has affected rice production worldwide and its effects are likely to become more devastating with the continuous increase in global temperatures, especially during the growing season. The bacterium can cause disease symptoms in different tissues and at different developmental stages. In reproductive stages, the bacterium interferes with grain development in the panicles and, as a result, directly affects rice yield. Currently, there are no methods to control the disease because chemical control is not effective and completely resistant cultivars are not available. Thus, a promising approach is the use of antagonistic microorganisms. In this work, we identified one strain of Pseudomonas protegens and one strain of B. cepacia with antimicrobial activity against B. glumae in vitro and in planta. We further characterized the antimicrobial activity of P. protegens and found that this activity is associated with bacterial secretions. Cell-free secretions from P. protegens inhibited the growth of B. glumae in vitro and also prevented B. glumae from causing disease in rice. Although the specific molecules associated with these activities have not been identified, these findings suggest that the secreted fractions from P. protegens could be harnessed as biopesticides to control bacterial panicle blight of rice.
New Drug Treats forms of Non–Small Cell Lung Cancer and Thyroid Cancer
Authors: Aschenbrenner Diane S.
Published: August 2020

Selpercatinib (Retevmo) has been approved to treat adults with metastatic RET fusion-positive non–small cell lung cancer, adults and children 12 years and older with advanced or metastatic RET-mutant medullary thyroid cancer, and adults and children 12 years and older with advanced or metastatic RET fusion-positive thyroid cancer who are radioactive iodine-refractory.
A Different Kind of Nurse
Authors: Resnick Kathleen
Published: August 2020

Losing a beloved profession—only to discover the profession has become part of you.
Academics in Absentia: An Opportunity to Rethink Conferences in the Age of Coronavirus Cancellations
Authors: Lessing Juan N. , Anderson Lauren R. , Mark Nicholas M. , Maggio Lauren A. , Durning Steven J.
Published: August 2020

The COVID-19 pandemic has caused major disruptions to the academic medicine community, including the cancellation of most medical and health professions conferences. In this Perspective, the authors examine both the short- and longer-term implications of these cancellations, including the effects on the professional development and advancement of junior faculty and learners. While the COVID-19 pandemic is new in 2020, impediments to conference attendance and participation are not. Cost, personal responsibilities at home, and clinical duties have always restricted attendance. The authors argue that the unprecedented hardships of this pandemic present a unique opportunity to reimagine how conferences can be conducted and to rethink what it means to be part of an academic community. While there are challenges with this digital transformation of academia, there are also undeniable opportunities: online abstracts and recorded presentations enable wider viewership, virtual sessions permit wider participation and greater interactivity, and the elimination of travel facilitates more diverse expert panel participation. The authors conclude with proposals for how conference organizers and participants can expand access by leveraging available distance learning technology and other virtual tools, both during the COVID-19 pandemic and beyond.
Principles of Motorized Internal Lengthening of Long Bones
Authors: Keshet Doron , Addar Abdullah , Bernstein Mitchell
Published: August 2020

Motorized intramedullary lengthening nails (ILNs) have revolutionized limb lengthening surgery and led to an expansion of indications utilizing them for both upper and lower limb lengthening, fracture compression, and nonunion treatment. There are biological and mechanical differences between using ILNs and using external fixators for lengthening surgery that the treating surgeon must be familiar with. Biological factors include regenerate quality, healing indices, and regenerate complications. Mechanical differences pertain to the lengthening axis, stability, and postoperative weight-bearing. Practical principles of ILNs use such as nail selection (entry point, nail length, lengthening nail problems), use of blocking screws, soft tissue releases (for nerve decompression, joint subluxation, and contractures) and physical therapy protocols are discussed.
Bone Transport With Internal Devices
Authors: Kähler Olesen Ulrik , Herzenberg John E.
Published: August 2020

Bone defects on a traumatic, infectious or malignant background are effectively treated by distraction osteogenesis with internal bone transport nails, improving patient comfort, reducing treatment time, and minimizing complications during a treatment course that has traditionally been long and burdensome. This article describes a patient selection, indications, devices, techniques, complications, and our suggested treatment protocol. The nails allow for combinations of transport and lengthening, avoiding the use of external fixators and their inherent drawbacks: pin track infection, scarring, and the inconvenience of carrying an external device for a prolonged time. Modern implants allow full weight-bearing during treatment. Meticulous surgical planning, infection prophylaxis, healthy soft tissues, vigorous training, and rehabilitation are essential for good outcomes.
Mitochondrial transfer from bone-marrow-derived mesenchymal stromal cells to chondrocytes protects against cartilage degenerative mitochondrial dysfunction in rats chondrocytes
Authors: Wang Rui , Maimaitijuma Talatibaike , Ma Yuan-Yuan , Jiao Yang , Cao Yong-Ping
Published: August 2020

Background

Previous studies have reported that mitochondrial dysfunction participates in the pathological process of osteoarthritis (OA). However, studies that improve mitochondrial function are rare in OA. Mitochondrial transfer from mesenchymal stem cells (MSCs) to OA chondrocytes might be a cell-based therapy for the improvement of mitochondrial function to prevent cartilage degeneration. This study aimed to determine whether MSCs can donate mitochondria and protect the mitochondrial function and therefore reduce cartilage degeneration.

Methods

Bone-marrow-derived mesenchymal stromal cells (BM-MSCs) were harvested from the marrow cavities of femurs and tibia in young rats. OA chondrocytes were gathered from the femoral and tibial plateau in old OA model rats. BM-MSCs and OA chondrocytes were co-cultured and mitochondrial transfer from BM-MSCs to chondrocytes was identified. Chondrocytes with mitochondria transferred from BM-MSCs were selected by fluorescence-activated cell sorting. Mitochondrial function of these cells, including mitochondrial membrane potential (Δψm), the activity of mitochondrial respiratory chain (MRC) enzymes, and adenosine triphosphate (ATP) content were quantified and compared to OA chondrocytes without mitochondrial transfer. Chondrocytes proliferation, apoptosis, and secretion ability were also analyzed between the two groups.

Results

Mitochondrial transfer was found from BM-MSCs to OA chondrocytes. Chondrocytes with mitochondrial from MSCs (MSCs + OA group) showed increased mitochondrial membrane potential compared with OA chondrocytes without mitochondria transfer (OA group) (1.79 ± 0.19 vs. 0.71 ± 0.12, t = 10.42, P < 0.0001). The activity of MRC enzymes, including MRC complex I, II, III, and citrate synthase was also improved (P < 0.05). The content of ATP in MSCs + OA group was significantly higher than that in OA group (161.90 ± 13.49 vs. 87.62 ± 11.07 nmol/mg, t = 8.515, P < 0.0001). Meanwhile, we observed decreased cell apoptosis (7.09% ± 0.68% vs.15.89% ± 1.30%, t = 13.39, P < 0.0001) and increased relative secretion of type II collagen (2.01 ± 0.14 vs.1.06 ± 0.11, t = 9.141, P = 0.0008) and proteoglycan protein (2.08 ± 0.20 vs. 0.97 ± 0.12, t = 8.227, P = 0.0012) in MSCs + OA group, contrasted with OA group.

Conclusions

Mitochondrial transfer from BM-MSCs provided protection for OA chondrocytes against mitochondrial dysfunction and degeneration through improving mitochondrial function, cell proliferation, and inhibiting apoptosis in chondrocytes. This finding may offer a new therapeutic direction for OA.
The Million Hearts Initiative
Authors: Wall Hilary K. , Stolp Haley , Wright Janet S. , Ritchey Matthew D. , Thomas Randal J. , Ades Philip A. , Sperling Laurence S.
Published: August 2020

Million Hearts and partners have been committed to raising national cardiac rehabilitation participation rates to a goal of 70%. Quality improvement tools, resources, and surveillance models have been developed in support. Efforts to enhance research programs and collaborative initiatives have created momentum to accelerate implementation of new care models.
Protocol-driven Antibiotic Treatment of Pediatric Empyema After Fibrinolysis
Authors: Svetanoff Wendy Jo , Dorman Robert M. , Dekonenko Charlene , Osuchukwu Obiyo , Jain Shubhika , Depala Kartik , Myers Angela , Oyetunji Tolulope A. , St Peter Shawn D.
Published: August 2020

Background:

The duration of antibiotic treatment after resolution of empyema in children is variable. We evaluated the efficacy and safety of a protocol-driven antibiotic regimen aimed to decrease antibiotic duration following treatment with fibrinolysis.

Methods:

Our institutional protocol consisted of 7 further days of antibiotics upon removal of the thoracostomy tube, with the patient being afebrile, off supplemental oxygen, and having negative cultures. A prospective observational study was then performed between September 2014 and March 2019. Empyema recurrence and antibiotic-related complications were recorded. Results were compared with previously published data from the preprotocol era.

Results:

A total of 37 patients were included. Mean total duration of antibiotics decreased from 26 ± 6.5 days in the preprotocol group to 22 ± 9.7 days in the postprotocol group (P = 0.004). This resulted in a significant decrease in hospital stay from the preprotocol cohort to the postprotocol cohort, respectively (9.3 ± 4.8 d versus 6.8 ± 3.1 d, P = 0.003). Sixty-two percentage of the patients were intended to treat according to the protocol, with a 50% adherence rate. Patients in which the protocol was followed had an average of 2.8 fewer days of antibiotics after discharge (P = 0.004), although overall duration was not statistically different. Significantly fewer antibiotic-related complications were noted after protocol initiation. There was no difference in empyema recurrence or readmissions.

Conclusions:

Institution of a protocol-driven approach to antibiotic duration following resolution of pleural space disease may reduce antibiotic duration and complications without reducing efficacy.
Fever Without an Apparent Source in Young Infants: A Multicenter Retrospective Evaluation of Adherence to the Dutch Guidelines
Authors: Klarenbeek Nikki N. , Keuning Maya , Hol Jeroen , Pajkrt Dasja , Plötz Frans B.
Published: August 2020

Background:

The Dutch fever without an apparent source (FWS) guidelines were published to timely recognize and treat serious infections. We determined the adherence to the Dutch FWS guidelines and the percentage of serious infections in infants younger than 3 months of age. Second, we identified which clinical criteria, diagnostic tests, and management were associated with nonadherence to the guidelines.

Methods:

A retrospective cohort study was performed in 2 Dutch teaching hospitals. We assessed the charts of all infants with FWS who presented at the emergency departments from September 30, 2017, to October 1, 2019. Diagnostic and therapeutic decisions were compared with the recommendations, as published in the Dutch guidelines. Infants were categorized into the nonadherence group in case 1 or more recommendations were not adhered to.

Results:

Data on 231 infants were studied; 51.5% of the cases adhered to the Dutch guidelines and 16.0% suffered from a serious infection. The percentage of infants with a serious infection was higher in the adherence compared with the nonadherence group. We observed no relevant differences in clinical outcomes. Univariate regression analysis showed that an abnormal white blood cell count was associated with nonadherence (OR 0.4, P = 0.049). Not obtaining a urine and blood culture and not starting intravenous antibiotic treatment were the most frequent reasons for nonadherence to the guidelines.

Conclusions:

Our study indicates that there was nonadherence in a large proportion of FWS cases. The guidelines may need to be adjusted to increase adherence.