bluuebunny/crossref_metadata_2025 huggingface dataset:
The trickle‐down effect of managers' belief in the importance of human resource management practices on employee performance: evidence from China
Authors: Jiang Jianwu , Li Shuling , Zhu Wenbo
Published: June 2022

Many studies have investigated the effects of human resource management practices on employee performance. Managers' belief in the importance of competent human resource management at the firm level and the department level influences its impact on employee performance, yet this has not been examined. Accordingly, based on the theory of upper echelons, this study empirically tested a trickle‐down effect model of managers' belief in HRM importance on employee performance. A cross‐level analysis was conducted using data collected from 56 top managers, 91 department supervisors and 316 employees in China. The results showed: (1) top managers' belief in human resource management importance positively influenced human resource management competence, which, in turn, played a fully mediating role between human resource management importance at the firm level and human resource management effectiveness at the departmental level; (2) the effectiveness of human resource management as evaluated by department supervisors exerted a significant positive influence on employees' human resource practices; and (3) the effectiveness of human resource management as evaluated by department supervisors indirectly affected employees' performance through their perceived human resource practices.
Decreased sperm counts in Swedish users of oral tobacco
Authors: Kimblad Agnes , Ollvik Gustav , Lindh Christian H , Axelsson Jonatan
Published: June 2022

Background

Smoke‐free tobacco via moist oral snuff (snus) is used daily in more than 20% of Swedish men. Negative effects of cigarette smoking on sperm parameters are well documented, unlike for snuff, despite relevance also for other smoke‐free nicotine products.

Objectives

We wanted to investigate whether reproductive parameters differed between users and non‐users of snuff, and whether the amount of snuff and nicotine exposure mattered.

Materials and methods

Men (n = 613) from the general population, recruited 2000–2010, were physically examined, answered questions on smoking and snuff use, and delivered urine, blood and semen samples. Sperm concentration, total sperm count, semen volume, percent morphologically normal and progressively motile sperm, and DNA fragmentation index (by the Sperm Chromatin Structure Assay) and reproductive hormones were analysed. Nicotine exposure was measured through urinary levels of cotinine. We used general linear models, with adjustments including cigarette smoking, and for semen parameters also abstinence time.

Results

After adjustments, total sperm count was 24% lower (P = 0.03) and testosterone 14% higher (P < 0.001) in 109 users of snuff than in non‐users, whereas cotinine was positively associated with testosterone and oestradiol (P < 0.001). Numbers of boxes of snuff used per week were associated with testosterone and FSH (P < 0.001).

Discussion

Applied to the general population, the consumption of smoke‐free tobacco by the use of snuff was associated with a lower sperm count and a higher testosterone, for which the extent seemed to play a role.

Conclusions

Independent of smoking, consumption of snuff was associated with lower total sperm count and different hormone levels. Applying these results to a reported association between sperm count and the chance of pregnancy, men who used snuff would have about a 10% lower chance of fathering a child.
Effect of perioperative lignocaine infusion on postoperative pain relief for laparoscopic intraperitoneal onlay mesh repair: A randomized controlled study
Authors: Sharma Bimla , Garg Rashi , Sahai Chand , Gupta Anjeleena Kumar , Gera Anjali , Sood Jayashree
Published: June 2022

Introduction

The focus on enhanced recovery after surgery (ERAS) and opioid‐free anesthesia has renewed interest in use of lignocaine. We evaluated postoperative pain relief following intravenous (IV) lignocaine administration in patients undergoing laparoscopic intraperitoneal onlay mesh repair (IPOM).

Methods

Seventy patients were randomized into two groups. Group L patients were administered IV lignocaine infusion (1.5 mg/kg) at induction of anesthesia followed by infusion (1.5 mg/kg/h), until 1 hour in the post‐anesthesia care unit (PACU). Group P patients received equal volumes of normal saline IV infusion. We recorded hemodynamics, perioperative analgesic consumption, postoperative visual analog scores (VAS), incidence of postoperative nausea and vomiting (PONV), bowel function, patient satisfaction and length of hospital stay (LOS).

Results

The hemodynamics in both groups were maintained. Group L had lower VAS scores as compared to Group P (P < .05). Intraoperative fentanyl consumption in Group L was significantly less than Group P (P = .029). Group L patients scored lower on the Likert scale in comparison to the patients of Group P at 0 hour (P = .013). Recovery of bowel function as assessed by time to pass first flatus was significantly shortened by IV lignocaine (P = .001). The perioperative administration of IV lignocaine resulted in decreased postoperative analgesic requirement and greater patient satisfaction scores.

Conclusions

Perioperative IV lignocaine infusion provided good pain relief, hemodynamic stability and decreased perioperative analgesic consumption. PONV incidence decreased along with an early return of bowel function, reduced LOS and improved patient satisfaction in patients undergoing laparoscopic IPOM surgery.
Frequency of benign neutropenia among Black versus White individuals undergoing a bone marrow assessment
Authors: Borinstein Scott C. , Agamasu David , Schildcrout Jonathan S. , Bastarache Lisa , Bagheri Minoo , Davis Lea K. , Roden Dan M. , Michael Stein C. , Van Driest Sara L. , Mosley Jonathan D.
Published: June 2022

Healthy individuals in the United States identified as having Black race have lower neutrophil counts, on average, than individuals identified as having White race, which could result in more negative diagnostic evaluations for neutropenia. To test this hypothesis, the proportion of evaluations where the final diagnosis was clinically insignificant neutropenia for Black and White individuals who underwent an evaluation by a haematologist that included a bone marrow (BM) biopsy to investigate neutropenia was assessed. 172 individuals without prior haematological diagnoses who underwent a haematological evaluation to investigate neutropenia. Individuals diagnosed with clinically insignificant neutropenia between Black and White individuals were compared using a propensity‐score‐adjusted logistic regression. Of 172 individuals, 42 (24%) were classified as Black race, 86 (50%) were males, and the 79 (46%) were over 18 years old. A BM biopsy did not identify pathology in 95% (40 of 42) of Black individuals and 68% (89 of 130) of White Individuals. Black individuals (25 of 42 [60%]) received a final diagnosis of clinically insignificant neutropenia, compared to White individuals (12 of 130 [9%]) (adjusted odds ratio =7.9, 95% CI: 3.1 – 21.1). We conclude that black individuals were more likely to receive a diagnosis of clinically insignificant neutropenia after haematological assessment.
Contamination effects on sexual selection in wild dung beetles
Authors: Villada‐Bedoya Sebastián , Córdoba‐Aguilar Alex , Escobar Federico , González‐Tokman Daniel
Published: June 2022

Sexual selection influences the expression of secondary sexual traits, which are costly to produce and maintain and are thus considered honest indicators of individual condition. Therefore, sexual selection could select for high‐quality individuals able to respond to stressful conditions, with impacts on population‐level fitness. We sampled dung beetles from 19 pastures and investigated if contamination by herbicides and veterinary drugs modifies male investment in sexually selected traits and has associated population‐level effects. We measured horn size, condition dependence (i.e. size‐corrected body mass) and allometry, besides abundance and sexual size dimorphism in three species: Copris incertus, Euoniticellus intermedius and Digitonthophagus gazella. In contrary to our expectations, horn size was independent of contamination and individual condition. However, strong positive allometric relationships were reduced by herbicide contamination for C. incertus and D. gazella and were increased by ivermectin for C. incertus, revealing differential investment in horn production according to body size in contaminated habitats. At the population level, large‐horned C. incertus males were more abundant in contaminated pastures, potentially revealing a case of evolutionary rescue by sexual selection or a plastic response to higher population densities. Finally, chemical compounds affected the sexual size dimorphism of all three species, with potential effects on female fecundity or intrasexual selection. Together, our findings indicate that contamination interferes with sexual selection processes in the wild, opening new questions regarding the role of sexual selection in favouring species persistence in contaminated environments.
The occurrence and feeding of a critically endangered shark species, Oxynotus centrina in the Sea of Marmara
Authors: Gül Güzin , Yokeş Mehmet Baki , Demirel Nazli
Published: June 2022

The angular roughshark, Oxynotus centrina (Linnaeus, 1758), is a rarely encountered deep‐sea demersal shark species. It is listed as “Critically Endangered” in the IUCN's regional assessment for the Mediterranean. Like other sharks and rays, the angular roughshark is subject to by‐catch in demersal trawl and longline fisheries. This study contributes new knowledge on (a) its occurrence, size and sex information; and (b) its feeding ecology in the Sea of Marmara. Data were collected on total length (TL), total weight (TW) and sex from unpublished research survey reports performed intermittently from 1994 to 2020. According to the data, O. centrina was mainly recorded from the muddy sand bottom type in the southwest region of the Marmara Sea, which has higher biodiversity of macrobenthic species than other regions. Different methodological approaches were conducted to understand its feeding, such as DNA metabarcoding and isotope analysis to identify its prey spectra and assign a trophic level. Sampled specimens were full of liquid in their stomachs without any discernible visually identifiable prey items. The metabarcoding analyses were also unsuccessful in identifying any prey items. Trophic position calculation based on nitrogen isotope in muscles highlighted that O. centrina has the highest trophic position compared to the other sharks and rays in the Sea of Marmara. Although it was found mainly feeding on polychaetes and sipunculids species from previous studies, the δ15N values made the authors cautious about the possibility of this species feeding on low trophic‐level benthic invertebrates. Because the authors could not observe the presence of shark vitellus in the stomachs and could not succeed in DNA identification for prey, this study highlights high δ15N values similar to top predators for O. centrina. The authors conclude that this species strategically feeds mainly on shark eggs to fulfil its nutritional requirements with minimum energy expenditure in line with its slow‐moving behaviour and mouth morphology.
Identification of virus infections of European eels intended for stocking measures
Authors: Danne Linna , Adamek Mikolaj , Wonnemann Hubert , Pieper Theresa , Fey Daniel , Hellmann John
Published: June 2022

The spread of viral diseases in eels is suggested to severely affect the European eel (Anguilla anguilla) panmictic population. The European Commission has initiated the Eel Recovery Plan (Council Regulation No. 1100/2007) to try to return the European eel stock to more sustainable levels within that measures eel restocking. However, scientific evidence evaluating the efficacy of stocking remains scarce. In addition, knowledge about the impact and contribution of eel stocking on the distribution of infectious diseases is insufficient. In this study, we aimed to investigate virus infections in batches of eels intended for restocking. We analysed samples of glass eels from certified fisheries and farmed European eels from different aquaculture farms. All analysed eels were purchased within a North Rhine Westphalian conservation program. Via a combination of cell culture and qPCR‐based techniques, we detected infections of glass eels with the rhabdovirus Eel Virus European X and anguillid herpesvirus 1 infections in farmed eels (10–15 cm).
Antibiotic, heavy metal, and disinfectant resistance in chicken, cattle, and sheep origin E. coli and whole‐genome sequencing analysis of a multidrug‐resistant E. coli O100:H25 strain
Authors: Cufaoglu Gizem , Cengiz Gorkem , Onaran Acar Bahar , Yesilkaya Busra , Ayaz Naim Deniz , Levent Gizem , Goncuoglu Muammer
Published: June 2022

In this study, antibiotic, heavy metal, and disinfectant resistance profiles of E. coli and E. coli O157 isolates were determined, and whole‐genome sequencing of a multidrug‐resistant E. coli O100:H25 strain was reported. A total of 70 E. coli isolated from chicken neck skin and sheep cecum samples, and 32 E. coli O157 strains isolated from cattle carcass, sheep carcass, and slaughterhouse wastewater samples were explored. Minimum inhibitory concentrations (MICs) of one antibiotics, eight heavy metals, and three disinfectants were determined by the broth microdilution method. Twenty of those isolates exhibiting high MIC values against compounds tested were further analyzed by PCR for the presence of relevant resistance genes (n = 42). The majority of the isolates tested were resistant to erythromycin and/or fosfomycin (99% and 78%, respectively) and 89% of the isolates were multidrug‐resistant. Among the heavy metals, and disinfectants that were quaternary ammonium compounds (QAC) tested, the highest prevalence of resistance was observed against nickel (71%) and followed by zinc (62%), and N‐alkyl‐dimethyl‐benzyl‐ammonium chloride (26%). While blaAmpC, ermC, murA, and aadA were the most abundant antibiotic resistance genes, rcnA and zntA, and mdfA, sugE (c), and ydg(F) were also commonly observed as heavy metal and disinfectant genes, respectively. Additionally, whole‐genome sequencing was performed for a single multidrug‐resistant strain (E. coli P91). This strain was identified as serotype O100:H25, and harbored three Inc class plasmids and ant(2″)‐Ia, aph(3′)‐Ia, aph(3″)‐Ib, aph(6)‐Id, blaTEM‐1A, dfrA5, mdf(A), sul1, sul2, and tet(A) genes along with the various heavy metal and disinfectant related genes. The findings of the study show that both phenotypic and genotypic antibiotic, heavy metal, and disinfectant resistance are highly prevalent in E. coli isolates that originated from food‐producing animals. The use of antimicrobials in food‐producing animals needs to be carefully evaluated since the coexistence of antibiotic, heavy metal, and disinfectant resistance genes may result in a coselection that yields the emergence and spread of highly persistent and resistant strains in agricultural settings.
Elderspeak communication and pain severity as modifiable factors to rejection of care in hospital dementia care
Authors: Shaw Clarissa A. , Ward Caitlin , Gordon Jean , Williams Kristine N. , Herr Keela
Published: June 2022

Background

Rejection of care (RoC) occurs when persons living with dementia (PLWD) withstand or oppose the efforts of their caregiver. Improvements in hospital dementia care are needed, and one way to address this need is by identifying factors that lead to RoC, particularly those that are modifiable. Elderspeak communication is an established antecedent to RoC among PLWD in nursing homes. The purpose of this study was to extend these results to acute care settings by determining the impact of elderspeak communication by nursing staff on RoC by hospitalized PLWD.

Methods

Care encounters between nursing staff and PLWD were audio‐recorded, transcribed verbatim, and coded for semantic, pragmatic, and prosodic features of elderspeak. RoC behaviors was scored in real‐time using the Resistiveness to Care Scale. A Bayesian repeated‐measures hurdle model was used to evaluate the association between elderspeak and both the presence and severity of RoC.

Results

Eighty‐eight care encounters between 16 PLWD and 53 nursing staff were audio‐recorded for elderspeak and scored for RoC. Nearly all (96.6%) of the encounters included some form of elderspeak. Almost half of the care encounters (48.9%) included RoC behaviors. A 10% decrease in elderspeak was associated with a 77% decrease in odds of RoC (OR = 0.23, 95% CI = 0.03, 0.68) and a 16% decrease ( 0.84, CI = 0.73, 0.96) in the severity of RoC. A one‐unit decrease in pain severity was associated with 73% reduced odds of RoC (OR = 0.27, CI = 0.12, 0.45) and a 28% decrease ( 0.72, CI = 0.64, 0.80) in the severity of RoC.

Conclusions

Both elderspeak by nursing staff and RoC by PLWD are present and pervasive in acute care. Pain and elderspeak are two modifiable factors of RoC in hospitalized PLWD. Person‐centered interventions are needed that address communication practices and pain management for hospitalized PLWD.
Screening, Treatment, and Monitoring of Iron Deficiency Anemia in Pregnancy and Postpartum
Authors: Elmore Christina , Ellis Jessica
Published: June 2022

Iron deficiency anemia is the most prevalent form of anemia worldwide. In the United States, clinicians routinely screen for iron deficiency anemia upon initiation of prenatal care, at the start of the third trimester, and prior to birth. Treatment of iron deficiency anemia generally begins with oral supplementation of elemental iron, which is associated with adverse gastrointestinal effects. These adverse effects can decrease adherence, leading to subtherapeutic treatment. Newer evidence highlights the benefits of early screening for iron deficiency before the onset of anemia, as well as the use of intravenous iron to expedite the treatment of iron deficiency anemia. More research is needed on the potential consequences of over‐supplementation and iron deficiency without anemia to guide treatment. This article reviews the evidence for best practices for screening, treatment, and continued monitoring of iron deficiency anemia during pregnancy and postpartum. Maternal, fetal, and neonatal implications are reviewed, as well as the risks and benefits of treatment options. Finally, an evidence‐based algorithm is proposed to guide clinicians on continued monitoring after treatment.
Opinions and experiences of healthcare professionals regarding structured virtual patient visits in ICUs: A qualitative study
Authors: Türkmen Emine , Kebapçı Ayda
Published: June 2022

Objectives

This study aimed to reveal the experiences of healthcare professionals regarding a structured Virtual Patient Visit (sVPV) program implemented in an ICU during the coronavirus disease 2019 (COVID‐19) pandemic and to share the process of establishing the program.

Design

This qualitative, exploratory study was conducted using a semi‐structured, in‐depth interview method.

Setting

The study was conducted in a university hospital ICU in Turkey (where a sVPV program was implemented) and comprised one physician, eight nurses, and one clerk who volunteered to participate in the study. The data were evaluated with content analysis, and themes and sub‐themes were determined.

Findings

Five themes and 13 subthemes were obtained: (1) an essential program during the pandemic, (2) contributing to patient's recovery, (3) family‐centered care, (4) innovativeness, and (5) sustainability.

Conclusion

The results show that the sVPV program is highly innovative and effective and contributed to positive patient outcomes and family‐centered care practices during the COVID‐19 pandemic. In addition, it was revealed that in order to conduct sVPVs effectively, organizational planning, such as legal processes, and the employment of experienced and competent healthcare professionals, should be well managed.

Clinical relevance

A well‐designed sVPV program specific to the setting alleviates anxiety among patients and family members, increases patient motivation and healing, and decreases the workloads of healthcare professionals. It is recommended that the sVPV program, which can be easily used during not only COVID‐19 pandemics but also during other crises, be adopted in all ICUs and carried out by a dedicated nurse or healthcare provider.
A blended eHealth intervention for insomnia following acquired brain injury: a randomised controlled trial
Authors: Ford Marthe E. , Geurtsen Gert J. , Groet Erny , Rambaran Mishre Radha D. , Van Bennekom Coen A. M. , Van Someren Eus J. W.
Published: June 2022

The high prevalence and severe consequences of poor sleep following acquired brain injury emphasises the need for an effective treatment. However, treatment studies are scarce. The present study evaluates the efficacy of blended online cognitive behavioural therapy for insomnia (eCBT‐I) developed specifically for people with acquired brain injury. In a multicentre prospective, open‐label, blinded end‐point randomised clinical trial, 52 participants with insomnia and a history of a stroke or traumatic brain injury were randomised to 6 weeks of guided eCBT‐I or treatment as usual, with a 6‐week follow‐up. The primary outcome measure was the change in insomnia severity between baseline and after treatment, measured with the Insomnia Severity Index. Results showed that insomnia severity improved significantly more with eCBT‐I than with treatment as usual compared to baseline, both at post‐treatment (mean [SEM] 4.0 [1.3] insomnia severity index points stronger decrease, d = 0.96, p < 0.003) and at follow‐up (mean [SEM] 3.2 [1.5] insomnia severity index points, d = −0.78, p < 0.03). In conclusion, our randomised clinical trial shows that blended CBT is an effective treatment for insomnia, and feasible for people with acquired brain injury, regardless of cognitive and psychiatric complaints. Online treatment has major advantages in terms of availability and cost and may contribute to the successful implementation of insomnia treatment for people with acquired brain injuries.
Comparison of a universal (but complex) model for avian egg shape with a simpler model
Authors: Shi Peijian , Gielis Johan , Niklas Karl J.
Published: June 2022

Recently, a universal equation by Narushin, Romanov, and Griffin (hereafter, the NRGE) was proposed to describe the shape of avian eggs. While NRGE can simulate the shape of spherical, ellipsoidal, ovoidal, and pyriform eggs, its predictions were not tested against actual data. Here, we tested the validity of the NRGE by fitting actual data of egg shapes and compared this with the predictions of our simpler model for egg shape (hereafter, the SGE). The eggs of nine bird species were sampled for this purpose. NRGE was found to fit the empirical data of egg shape well, but it did not define the egg length axis (i.e., the rotational symmetric axis), which significantly affected the prediction accuracy. The egg length axis under the NRGE is defined as the maximum distance between two points on the scanned perimeter of the egg's shape. In contrast, the SGE fitted the empirical data better, and had a smaller root‐mean‐square error than the NRGE for each of the nine eggs. Based on its mathematical simplicity and goodness‐of‐fit, the SGE appears to be a reliable and useful model for describing egg shape.
Spatial Linkages in Chinese Service and Manufacturing Outward Fdi: Empirical Evidence From the United States
Authors: He Lisha
Published: June 2022

The characteristics of neighbouring regions, namely third‐region effects, have become major determinants of location decision for FDI. The literature on spatial effects primarily focused on FDI from advanced economies, while it remains unclear to what extent the spatial effects have influenced the location of FDI by different industries from emerging economies in a host country. Using data on Mainland Chinese outward FDI in the United States at the state level from 2005 to 2017 and a spatial Durbin model, this study presents empirical evidence on the positive influence of third‐region effects on location decisions for Chinese OFDI. Specifically, Chinese OFDI in one state complements those in neighbouring states. In addition, manufacturing FDI tends to follow strategic asset seeking and is influenced by third‐region effects, whereas service FDI focuses more on market seeking. Finally, this study shows that social‐cultural networks considerably facilitate Mainland Chinese investments in overseas markets.
Phaeohyphomycosis caused by Phialophora americana in a dog
Authors: Martini Franco , Seehusen Frauke , Krudewig Christiane , Beckmann Katrin M. , Favrot Claude , Fischer Nina M. , Guenova Emmanuella , Rostaher Ana
Published: June 2022

Phaeohyphomycosis was diagnosed in a 6‐year‐old, male castrated Dachshund on immunosuppressive treatment. The fungus was identified by culture and PCR as Phialophora americana. This is the first reported case of infection with this pathogen in a dog. The infection was successfully managed medically, without surgical intervention.
Barriers to and Facilitators of Adherence to Prescribed Home Exercise in Older Adults at Risk of Falling in Singapore: A Qualitative Study
Authors: Teng Bernadine , Rosbergen Ingrid C.M. , Gomersall Sjaan R. , Hatton Anna , Brauer Sandra G.
Published: June 2022

Adherence to prescribed exercise poses significant challenges for older adults despite proven benefits. The aim of this exploratory descriptive qualitative study was to explore the perceived barriers to and facilitators of prescribed home exercise adherence in community-dwelling adults 65 years and older. Three focus groups with 17 older adults (Mage ± SD = 77 ± 5.12) living in Singapore were conducted. Inductive thematic analysis revealed that “the level of motivation” of individuals constantly influenced their exercise adherence (core theme). The level of motivation appeared to be a fluid concept and changed due to interactions with two subthemes: (a) individual factors (exercise needs to be tailored to the individual) and (b) environmental factors (i.e., support is essential). Hence, these factors must be considered when designing strategies to enhance exercise adherence in this vulnerable population. Strategies must be informed by the culturally unique context, in this case, a developed country with a multiethnic urban Asian population.
Evolving magma temperature and volatile contents over the 2008–2018 summit eruption of Kīlauea Volcano
Authors: Crozier Josh , Karlstrom Leif
Published: June 2022

Magma rheology and volatile contents exert primary and highly nonlinear controls on volcanic activity. Subtle changes in these magma properties can modulate eruption style and hazards, making in situ inference of their temporal evolution vital for volcano monitoring. Here, we study thousands of impulsive magma oscillations within the shallow conduit and lava lake of Kīlauea Volcano, Hawai‘i, USA, over the 2008–2018 summit eruptive sequence, encoded by “very-long-period” seismic events and ground deformation. Inversion of these data with a petrologically informed model of magma dynamics reveals significant variation in temperature and highly disequilibrium volatile contents over days to years, within a transport network that evolved over the eruption. Our results suggest a framework for inferring subsurface magma dynamics associated with prolonged eruptions in near real time that synthesizes petrologic and geophysical volcano monitoring approaches.
Spatial interplay patterns of cancer nuclei and tumor-infiltrating lymphocytes (TILs) predict clinical benefit for immune checkpoint inhibitors
Authors: Wang Xiangxue , Barrera Cristian , Bera Kaustav , Viswanathan Vidya Sankar , Azarianpour-Esfahani Sepideh , Koyuncu Can , Velu Priya , Feldman Michael D. , Yang Michael , Fu Pingfu , Schalper Kurt A. , Mahdi Haider , Lu Cheng , Velcheti Vamsidhar , Madabhushi Anant
Published: June 2022

Immune checkpoint inhibitors (ICIs) show prominent clinical activity across multiple advanced tumors. However, less than half of patients respond even after molecule-based selection. Thus, improved biomarkers are required. In this study, we use an image analysis to capture morphologic attributes relating to the spatial interaction and architecture of tumor cells and tumor-infiltrating lymphocytes (TILs) from digitized H&E images. We evaluate the association of image features with progression-free (PFS) and overall survival in non–small cell lung cancer (NSCLC) (
N
= 187) and gynecological cancer (
N
= 39) patients treated with ICIs. We demonstrated that the classifier trained with NSCLC alone was associated with PFS in independent NSCLC cohorts and also in gynecological cancer. The classifier was also associated with clinical outcome independent of clinical factors. Moreover, the classifier was associated with PFS even with low PD-L1 expression. These findings suggest that image analysis can be used to predict clinical end points in patients receiving ICI.
Gepotidacin is efficacious in a nonhuman primate model of pneumonic plague
Authors: Jakielaszek Charles , Hossain Mohammad , Qian Lian , Fishman Cindy , Widdowson Katherine , Hilliard Jamese J. , Mannino Frank , Raychaudhuri Aparna , Carniel Elisabeth , Demons Samandra , Heine Henry S. , Hershfield Jeremy , Russo Riccardo , Mega William M. , Revelli David , O’Dwyer Karen
Published: June 2022

Gepotidacin is a first-in-class triazaacenaphthylene antibacterial agent that selectively inhibits bacterial DNA gyrase and topoisomerase IV through a unique binding mode and has the potential to treat a number of bacterial diseases. Development of this new agent to treat pneumonic plague caused by
Yersinia pestis
depends on the U.S. Food and Drug Administration Animal Rule testing pathway, as testing in humans is not feasible. Here, preclinical studies were conducted in the African green monkey (AGM) inhalational model of pneumonic plague to test the efficacy of gepotidacin. AGMs infected with
Y. pestis
were dosed intravenously with gepotidacin (48, 36, or 28 milligrams/kilogram per day) for 10 days to provide a plasma concentration that would support a rationale for a 1000 mg twice or thrice daily intravenous dose in humans or saline as a control. The primary end point was AGM survival with predefined euthanasia criteria. Secondary end points included survival duration and bacterial clearance. Gepotidacin showed activity in vitro against diverse
Y. pestis
isolates including antibiotic-resistant strains. All control animals in the inhalational plague studies succumbed to plague and were blood culture and organ culture positive for
Y. pestis
. Gepotidacin provided a 75 to 100% survival benefit with all dose regimens. All surviving animals were blood culture and organ culture negative for
Y. pestis
. Our randomized, controlled efficacy trials in the AGM pneumonic plague nonhuman primate model together with the in vitro
Y. pestis
susceptibility data support the use of gepotidacin as a treatment for pneumonic plague caused by
Y. pestis
.
Targeting C3b/C4b and VEGF with a bispecific fusion protein optimized for neovascular age-related macular degeneration therapy
Authors: Yang Shiqi , Li Tong , Jia Huixun , Gao Min , Li Yiming , Wan Xiaoling , Huang Zhen , Li Min , Zhai Yuanqi , Li Xiaomeng , Yang Xiaotong , Wang Tao , Liang Jian , Gu Qing , Luo Xueting , Qian Lei , Lu Shujie , Liu Junjian , Song Yanping , Wang Fenghua , Sun Xiaodong , Yu Dechao
Published: June 2022

Antiangiogenesis therapies targeting vascular endothelial growth factor (VEGF) have revolutionized the treatment of neovascular ocular diseases, including neovascular age-related macular degeneration (nAMD). Compelling evidence has implicated the vital role of complement system dysregulation in AMD pathogenesis, implying it as a potential therapeutic strategy for geographic atrophy in dry AMD and to enhance the efficacy of anti-VEGF monotherapies in nAMD. This study reports the preclinical assessment and phase 1 clinical outcomes of a bispecific fusion protein, efdamrofusp alfa (code: IBI302), which is capable of neutralizing both VEGF isoforms and C3b/C4b. Efdamrofusp alfa showed superior efficacy over anti-VEGF monotherapy in a mouse laser-induced choroidal neovascularization (CNV) model after intravitreal delivery. Dual inhibition of VEGF and the complement activation was found to further inhibit macrophage infiltration and M2 macrophage polarization. Intravitreal efdamrofusp alfa demonstrated favorable safety profiles and exhibited antiangiogenetic efficacy in a nonhuman primate laser-induced CNV model. A phase 1 dose-escalating clinical trial (NCT03814291) was thus conducted on the basis of the preclinical data. Preliminary results showed that efdamrofusp alfa was well tolerated in patients with nAMD. These data suggest that efdamrofusp alfa might be effective for treating nAMD and possibly other complement-related ocular conditions.
The mechanosensitive ion channel PIEZO1 is expressed in tendons and regulates physical performance
Authors: Nakamichi Ryo , Ma Shang , Nonoyama Takayuki , Chiba Tomoki , Kurimoto Ryota , Ohzono Hiroki , Olmer Merissa , Shukunami Chisa , Fuku Noriyuki , Wang Guan , Morrison Errol , Pitsiladis Yannis P. , Ozaki Toshifumi , D’Lima Darryl , Lotz Martin , Patapoutian Ardem , Asahara Hiroshi
Published: June 2022

How mechanical stress affects physical performance via tendons is not fully understood. Piezo1 is a mechanosensitive ion channel, and E756del
PIEZO1
was recently found as a gain-of-function variant that is common in individuals of African descent. We generated tendon-specific knock-in mice using R2482H
Piezo1
, a mouse gain-of-function variant, and found that they had higher jumping abilities and faster running speeds than wild-type or muscle-specific knock-in mice. These phenotypes were associated with enhanced tendon anabolism via an increase in tendon-specific transcription factors, Mohawk and Scleraxis, but there was no evidence of changes in muscle. Biomechanical analysis showed that the tendons of R2482H
Piezo1
mice were more compliant and stored more elastic energy, consistent with the enhancement of jumping ability. These phenotypes were replicated in mice with tendon-specific R2482H
Piezo1
replacement after tendon maturation, indicating that PIEZO1 could be a target for promoting physical performance by enhancing function in mature tendon. The frequency of E756del
PIEZO1
was higher in sprinters than in population-matched nonathletic controls in a small Jamaican cohort, suggesting a similar function in humans. Together, this human and mouse genetic and physiological evidence revealed a critical function of tendons in physical performance, which is tightly and robustly regulated by PIEZO1 in tenocytes.
RNA-Based Therapy for Cryptosporidium parvum Infection: Proof-of-Concept Studies
Authors: Castellanos-Gonzalez A. , Sadiqova A. , Ortega-Mendez J. , White A. C.
Published: June 2022

Cryptosporidium
is a leading cause of moderate-to-severe diarrhea in children, which is one of the major causes of death in children under 5 years old. Nitazoxanide is the only FDA-approved treatment for cryptosporidiosis.
Development of an Enzyme-Linked Immunosorbent Assay for Detection of the Native Conformation of Enterovirus A71
Authors: Kingston Natalie J. , Grehan Keith , Snowden Joseph S. , Shegdar Mona , Fox Helen , Macadam Andrew J. , Rowlands David J. , Stonehouse Nicola J.
Published: June 2022

EVA71 is a medically important virus that is commonly associated with HFMD, resulting in periodic outbreaks, significant economic impact, and loss of life. Vaccination offers the potential to curtail future outbreaks, and vaccine development has been increasingly the focus of global research efforts.
Phylogeography of the White-Toothed Shrews Crocidura suaveolens and Crocidura sibirica: Searching for the Geographical Homeland
Authors: Gritsyshin V. A. , Artyushin I. V. , Burskaya V. O. , Sheftel B. I. , Lebedev V. S. , Bannikova A. A.
Published: June 2022

We studied the polymorphism of the cytb gene in two forms of the Lesser White-toothed Shrew species complex: Crocidura suaveolens s. stricto and C. sibirica. The haplotypes of C. sibirica are found to be very similar to those of Crocidura suaveolens. They do not belong to a distinct haplogroup. The molecular diversity of the populations in the Asian part of the range is higher than in Eastern Europe. For the combined sample from Asia and Europe together, we revealed a significant signal of population expansion. Analysis of the expansion time showed that the Asian territory was colonized earlier (before the last glacial maximum) than the Eastern Europe (at the very end of the Late Pleistocene and in the early Holocene). The results of the ancestral area reconstruction are consistent with the hypothesis of a Middle Asian origin of the C. suaveolens/C. sibirica group, recent colonization of Inner Asia and later penetration into Eastern Europe.
Family experiences with palliative care in freestanding paediatric hospices: a scoping review
Authors: Dorman Jennifer , Raffin Bouchal Shelley , daSilva Curiel Kathryn , Miller Megan
Published: June 2022

Background

Paediatric palliative care provides supportive care to children with life-threatening or life-limiting illnesses throughout the disease trajectory. Up to 42% of children receiving palliative care in Canada will die within a freestanding paediatric hospice or designated end-of-life care bed. Few studies have assessed families’ experiences of this care within freestanding paediatric hospices.

Objectives

To find and describe literature relating to family experiences in paediatric hospice palliative care throughout the end-of-life care journey including grief and bereavement.

Criteria

Inclusion criteria: Children antepartum to 18 years or older if on paediatric palliative care service. Research conducted in freestanding paediatric hospices that focused on families’ experiences and perceptions of end-of-life and grief and bereavement care. Full-text articles available in English.

Exclusion criteria: Adult palliative and end-of-life care, respite care, palliative care provided in acute or community settings, professional perspectives, unexpected or sudden child death, pregnancy after loss.

Sources of evidence

Academic Search Complete, CINAHL, Cochrane Database of Systematic Reviews, Embase, PsycINFO, PubMed and Web of Science databases were searched from database inception until the present. Grey literature was also searched for relevant results.

Charting methods

The scoping review was guided by recommendations from Arksey and O’Malley and Levacet al.

Results

A total of 4250 papers were retrieved, of which 10 met the scoping review criteria. The majority of studies were conducted in the UK. Three major themes emerged: more supportive care for families including grief and bereavement support, the hospice experience itself and future research areas.

Conclusions

There is little literature that focuses specifically on the needs of families within freestanding paediatric hospices. Further examination of the themes identified above provides an opportunity for future research.
Community-based anticipatory prescribing during COVID-19: a qualitative study
Authors: Antunes Bárbara Costa Pereira , Bowers Ben , Barclay Stephen , Gallagher Joshua , Conci Riccardo , Polak Louisa
Published: June 2022

Objectives

To understand healthcare professionals’ experiences of delivering anticipatory prescribing (AP) during the first wave of the UK COVID-19 pandemic.

Methods

Semistructured qualitative interviews were conducted with a purposive sample of 16 healthcare professionals involved in community palliative care. Data were analysed inductively using thematic analysis.

Results

Some of practitioners’ fears about the pandemic’s impact on delivering AP had not been realised during the first wave. Among patients with COVID-19 for whom community end-of-life care was deemed appropriate, deaths were perceived to be relatively easy to palliate with standard medications. These deaths were typically too rapid for AP to be appropriate or feasible. For non-COVID deaths, providing timely AP was more challenging: although community nurses and some palliative specialists continued to visit patients regularly, general practitioners did many fewer visits, moving abruptly to mainly remote consultations. This left some community nurses feeling undersupported, and prompted some palliative specialists to increase their direct involvement in AP. Several other changes were widely welcomed: collaboration to maintain drug supplies, adoption of online meetings and paperless practice, enhanced specialist helplines and a new policy allowing reuse of medication in care homes. The inclusion of more non-injectable options in AP protocols allowed clinicians to offer selected patients more choice, but few had yet done this in practice. No participants reported changing their prepandemic practice regarding administration of AP by lay caregivers.

Conclusions

Accomplishing AP during a pandemic was challenging, requiring healthcare professionals to make rapid changes to their systems and practices. Some changes may produce lasting improvements.
Clinical frailty and performance scale translation in palliative care: scoping review
Authors: Dewhurst Felicity , Stow Daniel , Paes Paul , Frew Katherine , Hanratty Barbara
Published: June 2022

Background

Frailty is associated with advancing age and increases the risk of adverse outcomes and death. Routine assessment of frailty is becoming more common in a number of healthcare settings, but not in palliative care, where performance scales (eg, the Australia-modified Karnofsky Performance Status Scale (AKPS)) are more commonly employed. A shared understanding of performance and frailty measures could aid interspecialty collaboration in both end-of-life care research and clinical practice.

Aims

To identify and synthesise evidence comparing measures of performance routinely collected in palliative care with the Clinical Frailty Scale (CFS), and create a conversion chart to support interspecialty communication.

Methods

A scoping literature review with comprehensive searches of PubMed, Web of Science, Ovid SP, the Cochrane Library and reference lists. Eligible articles compared the CFS with the AKPS, Palliative Performance Scale (PPS), Karnofsky Performance Scale or Eastern Cooperative Oncology Group Performance Status or compared these performance scales, in patients aged>18 in any setting.

Results

Searches retrieved 3124 articles. Two articles directly compared CFS to the PPS. Thirteen studies translated between different performance scores, facilitating subsequent conversion to CFS, specifically: AKPS/PPS 10/20=very severe frailty, AKPS/PPS 30=severe frailty, AKPS/PPS 40/50=moderate frailty, AKPS/PPS60=mild frailty.

Conclusion

We present a tool for converting between the CFS and performance measures commonly used in palliative care. A small number of studies provided evidence for the direct translation between CFS and the PPS. Therefore, more primary evidence is needed from a wider range of population settings, and performance measures to support this conversion.
Unifying theory of carotid plaque disruption based on structural phenotypes and forces expressed at the lumen/wall interface
Authors: Savastano Luis , Mousavi Hossein , Liu Yang , Khalsa Siri Sahib S , Zheng Yihao , Davis Evan , Reddy Adithya , Brinjikji Waleed , Bhambri Ankur , Cockrum Joshua , Pandey Aditya S , Thompson B Gregory , Gordon David , Seibel Eric J , Yonas Howard
Published: June 2022

Objectives

To integrate morphological, haemodynamic and mechanical analysis of carotid atheroma driving plaque disruption.

Materials and methods

First, we analysed the phenotypes of carotid endarterectomy specimens in a photographic dataset A, and matched them with the likelihood of preoperative stroke. Second, laser angioscopy was used to further define the phenotypes in intact specimens (dataset B) and benchmark with histology. Third, representative vascular geometries for each structural phenotype were analysed with Computational Fluid Dynamics (CFD), and the mechanical strength of the complicated atheroma to resist penetrating forces was quantified (n=14).

Results

In dataset A (n=345), ulceration (fibrous cap disruption) was observed in 82% of all plaques, intraplaque haemorrhage in 68% (93% subjacent to an ulcer) and false luminal formation in 48%. At least one of these ‘rupture’ phenotypes was found in 97% of symptomatic patients (n=69) compared with 61% in asymptomatic patients. In dataset B (n=30), laser angioscopy redemonstrated the structural phenotypes with near-perfect agreement with histology. In CFD, haemodynamic stress showed a large pulse magnitude, highest upstream to the point of maximal stenosis and on ulceration the inflow stream excavates the necrotic core cranially and then recirculates into the true lumen. Based on mechanical testing (n=14), the necrotic core is mechanically weak and penetrated by the blood on fibrous cap disruption.

Conclusions

Fibrous cap ulceration, plaque haemorrhage and excavation are sequential phenotypes of plaque disruption resulting from the chiselling effect of haemodynamic forces over unmatched mechanical tissue strength. This chain of events may result in thromboembolic events independently of the degree of stenosis.
Landform mapping, elevation modelling, and thaw subsidence estimation for permafrost terrain using a consumer-grade remotely-piloted aircraft
Authors: Oldenborger Greg A. , Bellehumeur-Génier O. , LeBlanc Anne-Marie , McMartin I.
Published: June 2022

We assess performance of a small consumer-grade remotely-piloted aircraft (RPA) for landform mapping, elevation modelling, and thaw subsidence estimation in continuous permafrost terrain. We acquired RPA imagery near Rankin Inlet, Nunavut, to construct orthomosaics and digital elevation models (DEMs) that we use to interpret geomorphology and surficial geology. We estimate seasonal thaw subsidence using DEM differences. To quantify accuracy, RPA DEMs are compared with a satellite-based reference elevation. Subsidence estimates are compared with measurements from differential interferometric synthetic aperture radar (DInSAR). We find that RPA images are very effective for mapping periglacial landforms and surficial geology with the chosen flight specifications. The DEMs exhibit vertical mean absolute error of approximately 1 cm at ground control points. Away from control points, relative vertical accuracy is approximately 3 cm. Comparison to the reference elevation results in survey-wide vertical mean absolute errors of 33–66 cm with high variability and spatial autocorrelation of elevation discrepancy. There is local agreement between DEM differences, DInSAR, and on-the-ground measurements of seasonal subsidence. Results suggest that small RPA may be applicable for mapping thaw subsidence on the order of a few centimetres near control points. However, DEM differences are influenced by vegetation and are contaminated by spatially-variable artefacts, preventing reliable survey-wide RPA estimation of seasonal thaw subsidence.