bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transcription factor-like 5 is a potential DNA- and RNA-binding protein essential for maintaining male fertility in mice
Authors: Xu Weiya , Zhang Yiyun , Qin Dongdong , Gui Yiqian , Wang Shu , Du Guihua , Yang Fan , Li Lufan , Yuan Shuiqiao , Wang Mei , Wu Xin 
Published: December 2021

ABSTRACT
Transcription factor-like 5 (TCFL5) is a testis-specific protein that contains the basic helix-loop-helix domain, but the in vivo functions of TCFL5 remain unknown. Herein, we generated CRISPR/Cas9-mediated knockout mice to dissect the function of TCFL5 in mouse testes. Surprisingly, we found that it was difficult to generate homozygous mice with the Tcfl5 deletion as the heterozygous males (Tcfl5+/−) were infertile. However, we did observe markedly abnormal phenotypes of spermatids and spermatozoa in the testes and epididymides of Tcfl5+/− mice. Mechanistically, we demonstrated that TCFL5 transcriptionally and post-transcriptionally regulated a set of genes participating in male germ cell development via TCFL5 ChIP-DNA and eCLIP-RNA high-throughput sequencing. We also identified a known RNA-binding protein, FXR1, as an interacting partner of TCFL5 that may coordinate the transition and localization of TCFL5 in the nucleus. Collectively, we herein report for the first time that Tcfl5 is haploinsufficient in vivo and acts as a dual-function protein that mediates DNA and RNA to regulate spermatogenesis.
This article has an associated First Person interview with the first author of the paper.
Energetic costs of ectoparasite infection in Atlantic salmon
Authors: Hvas Malthe , Bui Samantha 
Published: December 2021

ABSTRACT
Parasites are widespread in nature, where they affect the energy budget of hosts, and depending on the imposed pathogenic severity, this may reduce host fitness. However, the energetic costs of parasite infections are rarely quantified. In this study, we measured metabolic rates in recently seawater adapted Atlantic salmon (Salmo salar) infected with the ectoparasitic copepod Lepeophtheirus salmonis and used an aerobic scope framework to assess the potential ecological impact of this parasite–host interaction. The early chalimus stages of L. salmonis did not affect either standard or maximum metabolic rates. However, the later mobile pre-adult stages caused an increase in both standard and maximum metabolic rate yielding a preserved aerobic scope. Notably, standard metabolic rates were elevated by 26%, presumably caused by increased osmoregulatory burdens and costs of mobilizing immune responses. The positive impact on maximum metabolic rates was unexpected and suggests that fish are able to transiently overcompensate energy production to endure the burden of parasites and thus allow for continuation of normal activities. However, infected fish are known to suffer reduced growth, and this suggests that a trade-off exists in acquisition and assimilation of resources despite an uncompromised aerobic scope. As such, when assessing impacts of environmental or biotic factors, we suggest that elevated routine costs may be a stronger predictor of reduced fitness than the available aerobic scope. Furthermore, studying the effects on parasitized fish in an ecophysiological context deserves more attention, especially considering interacting effects of other stressors in the Anthropocene.
Severe hypoxia exposure inhibits larval brain development but does not affect the capacity to mount a cortisol stress response in zebrafish
Authors: Mikloska Kristina V. , Zrini Zoe A. , Bernier Nicholas J. 
Published: December 2021

ABSTRACTFish nursery habitats are increasingly hypoxic and the brain is recognized as highly hypoxia sensitive, yet there is a lack of information on the effects of hypoxia on the development and function of the larval fish brain. Here, we tested the hypothesis that by inhibiting brain development, larval exposure to severe hypoxia has persistent functional effects on the cortisol stress response in zebrafish (Danio rerio). Exposing 5 days post-fertilization (dpf) larvae to 10% dissolved O2 (DO) for 16 h only marginally reduced survival, but it decreased forebrain neural proliferation by 55%, and reduced the expression of neurod1, gfap and mbpa, markers of determined neurons, glia and oligodendrocytes, respectively. The 5 dpf hypoxic exposure also elicited transient increases in whole-body cortisol and in crf, uts1 and hsd20b2 expression, key regulators of the endocrine stress response. Hypoxia exposure at 5 dpf also inhibited the cortisol stress response to hypoxia in 10 dpf larvae and increased hypoxia tolerance. However, 10% DO exposure at 5 dpf for 16 h did not affect the cortisol stress response to a novel stressor in 10 dpf larvae or the cortisol stress response to hypoxia in adult fish. Therefore, while larval exposure to severe hypoxia can inhibit brain development, it also increases hypoxia tolerance. These effects may transiently reduce the impact of hypoxia on the cortisol stress response but not its functional capacity to respond to novel stressors. We conclude that the larval cortisol stress response in zebrafish has a high capacity to cope with severe hypoxia-induced neurogenic impairment.
Shortening the preparation time of the single prolonged breath-hold for radiotherapy sessions
Authors: Parkes Michael John , Green Stuart , Cashmore Jason , Ghafoor Qamar , Clutton-Brock Thomas 
Published: December 2021

Objective:
Single prolonged breath-holds of &gt;5 min can be obtained in cancer patients. Currently, however, the preparation time in each radiotherapy session is a practical limitation for clinical adoption of this new technique. Here, we show by how much our original preparation time can be shortened without unduly compromising breath-hold duration.

Methods:
44 healthy subjects performed single prolonged breath-holds from 60% O2 and mechanically induced hypocapnia. We tested the effect on breath-hold duration of shortening preparation time (the durations of acclimatization, hyperventilation and hypocapnia) by changing these durations and or ventilator settings.

Results:
Mean original breath-hold duration was 6.5 ± 0.2 (standard error) min. The total original preparation time (from connecting the facemask to the start of the breath-hold) was 26 ± 1 min. After shortening the hypocapnia duration from 16 to 5 min, mean breath-hold duration was still 6.1 ± 0.2 min (ns vs the original). After abolishing the acclimatization and shortening the hypocapnia to 1 min (a total preparation time now of 9 ± 1 min), a mean breath-hold duration of &gt;5 min was still possible (now significantly shortened to 5.2 ± 0.6 min, p &lt; 0.001). After shorter and more vigorous hyperventilation (lasting 2.7 ± 0.3 min) and shorter hypocapnia (lasting 43 ± 4 s), a mean breath-hold duration of &gt;5 min (5.3 ± 0.2 min, p &lt; 0.05) was still possible. Here, the final total preparation time was 3.5 ± 0.3 min.

Conclusions:
These improvements may facilitate adoption of the single prolonged breath-hold for a range of thoracic and abdominal radiotherapies especially involving hypofractionation.

Advances in knowledge:
Multiple short breath-holds improve radiotherapy for thoracic and abdominal cancers. Further improvement may occur by adopting the single prolonged breath-hold of &gt;5 min. One limitation to clinical adoption is its long preparation time. We show here how to reduce the mean preparation time from 26 to 3.5 min without compromising breath-hold duration
Correlation between contrast-enhanced cone-beam breast computed tomography features and prognostic staging in breast cancer
Authors: Ma Wei-mei , Li Jiao , Chen Shuang-gang , Cai Pei-qiang , Chen Shen , Chen Jie-ting , Zhou Chun-yan , He Ni , Wu Yaopan 
Published: December 2021

Objective:
To evaluate whether contrast-enhanced cone-beam breast CT (CE-CBBCT) features can risk-stratify prognostic stage in breast cancer.

Methods:
Overall, 168 biopsy-proven breast cancer patients were analysed: 115 patients in the training set underwent scanning using v. 1.5 CE-CBBCT between August 2019 and December 2019, whereas 53 patients in the test set underwent scanning using v. 1.0 CE-CBBCT between May 2012 and August 2014. All patients were restaged according to the American Joint Committee on Cancer eighth edition prognostic staging system. Following the combination of CE-CBBCT imaging parameters and clinicopathological factors, predictors that were correlated with stratification of prognostic stage via logistic regression were analysed. Predictive performance was assessed according to the area under the receiver operating characteristic curve (AUC). Goodness-of-fit of the models was assessed using the Hosmer-Lemeshow test.

Results:
As regards differentiation between prognostic stage (PS) I and II/III, increased tumour-to-breast volume ratio (TBR), rim enhancement pattern, and the presence of penetrating vessels were significant predictors for PS II/III disease (p &lt; 0.05). The AUCs in the training and test sets were 0.967 [95% confidence interval (CI) 0.938–0.996; p &lt; 0.001] and 0.896 (95% CI, 0.809–0.983; p = 0.001), respectively. Two features were selected in the training set of PS II vs III, including tumour volume [odds ratio (OR)=1.817, p = 0.019] and calcification (OR = 4.600, p = 0.040), achieving an AUC of 0.790 (95% CI, 0.636–0.944, p = 0.001). However, there was no significant difference in the test set of PS II vs III (P＞0.05).

Conclusion:
CE-CBBCT imaging biomarkers may provide a large amount of anatomical and radiobiological information for the pre-operative distinction of prognostic stage.

Advances in knowledge:
CE-CBBCT features have distinctive promise for stratification of prognostic stage in breast cancer.
Optimal Scheduling of Proactive Service with Customer Deterioration and Improvement
Authors: Hu Yue , Chan Carri W. , Dong Jing 
Published: December 2021

Service systems are typically limited resource environments where scarce capacity is reserved for the most urgent customers. However, there has been a growing interest in the use of proactive service when a less urgent customer may become urgent while waiting. On one hand, providing service for customers when they are less urgent could mean that fewer resources are needed to fulfill their service requirement. On the other hand, using limited capacity for customers who may never need the service in the future takes the capacity away from other more urgent customers who need it now. To understand this tension, we propose a multiserver queueing model with two customer classes: moderate and urgent. We allow customers to transition classes while waiting. In this setting, we characterize how moderate and urgent customers should be prioritized for service when proactive service for moderate customers is an option. We identify an index, the modified [Formula: see text]-index, which plays an important role in determining the optimal scheduling policy. This index lends itself to an intuitive interpretation of how to balance holding costs, service times, abandonments, and transitions between customer classes. This paper was accepted by David Simchi-Levi, stochastic models and simulation.
Profitability and Financial Leverage: Evidence from a Quasi-Natural Experiment
Authors: Heath Davidson , Sertsios Giorgo 
Published: December 2021

The relationship between profitability and leverage is controversial in the capital structure literature. We revisit this relation in light of a novel quasi-natural experiment that increases market power for a subset of firms. We find that treated firms increase their profitability throughout the treatment period. However, they only transiently reduce financial leverage, gradually reverting to their preshock level. Firms respond differently according to size with large firms gradually adjusting their leverage toward a new target and small firms reducing it. The patterns are broadly consistent with dynamic trade-off models with both fixed and variable adjustment costs. This paper was accepted by Gustavo Manso, finance. Supplemental Material: The online appendix and data are available at https://doi.org/10.1287/mnsc.2021.4235 .
Use of the PROMIS Mobility score in assessing function in adolescents and adults previously affected by childhood hip disease
Authors: Luo Weisang , Ali Mohammed S. , Limb Richard , Cornforth Christine , Perry Daniel C. 
Published: December 2021

Aims The Patient-Reported Outcomes Measurement Information System (PROMIS) has demonstrated faster administration, lower burden of data capture and reduced floor and ceiling effects compared to traditional Patient Reported Outcomes Measurements (PROMs). We investigated the suitability of PROMIS Mobility score in assessing physical function in the sequelae of childhood hip disease. Methods In all, 266 adolscents (aged ≥ 12 years) and adults were identified with a prior diagnosis of childhood hip disease (either Perthes’ disease (n = 232 (87.2%)) or Slipped Capital Femoral Epiphysis (n = 34 (12.8%)) with a mean age of 27.73 years (SD 12.24). Participants completed the PROMIS Mobility Computer Adaptive Test, the Non-Arthritic Hip Score (NAHS), EuroQol five-dimension five-level questionnaire, and the Numeric Pain Rating Scale. We investigated the correlation between the PROMIS Mobility and other tools to assess use in this population and any clustering of outcome scores. Results There was a strong correlation between the PROMIS Mobility and other established PROMs; NAHS ( rs = 0.79; p < 0.001). There was notable clustering in PROMIS at the upper end of the distribution score (42.5%), with less seen in the NAHS (20.3%). However, the clustering was broadly similar between PROMIS Mobility and the comparable domains of the NAHS; function (53.6%), and activity (35.0%). Conclusion PROMIS Mobility strongly correlated with other tools demonstrating convergent construct validity. There was clustering of physical function scores at the upper end of the distributions, which may reflect truncation of the data caused by participants having excellent outcomes. There were elements of disease not captured within PROMIS Mobility alone, and difficulties in differentiating those with the highest levels of function. Cite this article: Bone Jt Open 2021;2(12):1089–1095.
Significant reduction of patellar height affected lower clinical outcomes and knee flexion over five-year follow-up after total knee arthroplasty
Authors: Suthar Ashish , Yukata Kiminori , Azuma Yoshikazu , Suetomi Yutaka , Yamazaki Kazuhiro , Seki Kazushige , Sakai Takashi , Fujii Hiroshi 
Published: December 2021

Aims This study aimed to investigate the relationship between changes in patellar height and clinical outcomes at a mean follow-up of 7.7 years (5 to 10) after fixed-bearing posterior-stabilized total knee arthroplasty (PS-TKA). Methods We retrospectively evaluated knee radiographs of 165 knees, which underwent fixed-bearing PS-TKA with patella resurfacing. The incidence of patella baja and changes in patellar height over a minimum of five years of follow-up were determined using Insall-Salvati ratio (ISR) measurement. We examined whether patella baja (ISR < 0.8) at final follow-up affected clinical outcomes, knee joint range of motion (ROM), and Knee Society Score (KSS). We also assessed inter- and intrarater reliability of ISR measurements and focused on the relationship between patellar height reduction beyond measurement error and clinical outcomes. Results The ISR gradually decreased over five years after TKA, and finally 33 patients (20.0%) had patella baja. Patella baja at the final follow-up was not related to passive knee ROM or KSS. Interestingly, when we divided into two groups - patella baja and patella normal-alta (ISR ≥ 0.8) - the patella baja group already had a lower patellar height before surgery, compared with the patella normal-alta group. The ISR measurement error in this study was 0.17. Both passive knee flexion and KSS were significantly decreased in the group with a decrease in ISR of ≥ 0.17 at final follow-up. Conclusion Patellar height gradually decreased over five years of follow-up after TKA. The reduction in patellar height beyond measurement error following TKA was associated with lower clinical outcomes. Cite this article: Bone Jt Open 2021;2(12):1075–1081.
Coarse-to-fine optical MEMS accelerometer design and simulation
Authors: Rahimi Mojtaba , Taghavi Majid , Malekmohammad Mohammad 
Published: December 2021

A coarse-to-fine optical microelectromechanical systems (MEMS) accelerometer based on the Fabry–Pérot (FP) interferometer is proposed. The mechanical structure consists of a proof mass that is suspended by four L-shaped springs. The deflection of the proof mass due to the applied acceleration is detected using two FP cavities that comprise the system’s optical system. Using coarse-to-fine measurement and the dual wavelength method simultaneously increases the sensitivity of the accelerometer as well as the linear measurement range. The optical simulation shows that the sensitivity of the proposed device is 10 times as high as that of a similar optical MEMS accelerometer with one FP cavity. In addition, the proposed optical system is insensitive to the displacements of the proof mass in the orthogonal directions, which considerably reduced the cross-axis sensitivity. The minimum feature size of the structure is 15 µm and the optical signal is conducted completely through the optical fibers, facilitating the device fabrication. Here are the results of the simulation: mechanical sensitivity of 190 nm/g, optical sensitivity of 8 nm/g, linear measurement of

±
5

g

, and first resonance frequency of 1141 Hz.
Adopting a multidisciplinary telemedicine intervention for fall prevention in Parkinson’s disease. Protocol for a longitudinal, randomized clinical trial
Authors: Cubo Esther , Garcia-Bustillo Alvaro , Arnaiz-Gonzalez Alvar , Ramirez-Sanz Jose Miguel , Garrido-Labrador Jose Luis , Valiñas Florita , Allende Marta , Gonzalez-Bernal Jeronimo Javier , Gonzalez-Santos Josefa , Diez-Pastor José Francisco , Jahouh Maha , Arribas Jana , Trejo Jose 
Published: December 2021

Background
Approximately 40–70% of people with Parkinson’s disease (PD) fall each year, causing decreased activity levels and quality of life. Current fall-prevention strategies include the use of pharmacological and non-pharmacological therapies. To increase the accessibility of this vulnerable population, we developed a multidisciplinary telemedicine program using an Information and Communication Technology (ICT) platform. We hypothesized that the risk for falling in PD would decrease among participants receiving a multidisciplinary telemedicine intervention program added to standard office-based neurological care.

Objective
To determine the feasibility and cost-effectiveness of a multidisciplinary telemedicine intervention to decrease the incidence of falls in patients with PD.

Methods
Ongoing, longitudinal, randomized, single-blinded, case-control, clinical trial. We will include 76 non-demented patients with idiopathic PD with a high risk of falling and limited access to multidisciplinary care. The intervention group (n = 38) will receive multidisciplinary remote care in addition to standard medical care, and the control group (n = 38) standard medical care only. Nutrition, sarcopenia and frailty status, motor, non-motor symptoms, health-related quality of life, caregiver burden, falls, balance and gait disturbances, direct and non-medical costs will be assessed using validated rating scales.

Results
This study will provide a cost-effectiveness assessment of multidisciplinary telemedicine intervention for fall reduction in PD, in addition to standard neurological medical care.

Conclusion
In this challenging initiative, we will determine whether a multidisciplinary telemedicine intervention program can reduce falls, as an alternative intervention option for PD patients with restricted access to multidisciplinary care.

Trial registration
ClinicalTrials.gov Identifier: NCT04694443.
‘It is a disease which comes and kills directly’: What refugees know about COVID-19 and key influences of compliance with preventive measures
Authors: Lusambili Adelaide M. , Martini Michela , Abdirahaman Faiza , Abena Asante , Guni Joseph N. , Ochieng Sharon , Luchters Stanley 
Published: December 2021

Background
Refugees are at increased risk for COVID-19 infection in part due to their living conditions, which make it harder to adopt and adhere to widely accepted preventive measures. Little empirical evidence exists about what refugees know about COVID-19 and what they do to prevent infection. This study explored what refugee women and their health care workers understand about COVID-19 prevention, the extent of their compliance to public health recommendations, and what influences the adoption of these measures.

Methods
In October 2020, we conducted 25 in-depth interviews with facility and community health care staff (n = 10) and refugee women attending antenatal and postnatal care services (n = 15) in Eastleigh, Nairobi.

Findings
While researchers found a high level of awareness about COVID-19 and related prevention and control measures among refugee women, various barriers affected compliance with such measures, due in part to poverty and in part to rampant misconceptions informed by religious beliefs and political narratives about the virus.

Conclusions
These findings indicated that Kenya’s Ministry of Health needs to institute a concerted and continuous education program to bring refugee communities up to speed about COVID-19 and its prevention. In addition to disseminating information about the need to wear masks and repeatedly wash hands, supplies—masks, soap and access to water—need to be made available to poor refugee communities. Future research could explore which measures for disseminating factual information work best in refugee populations with different cultural norms and how best to target interventions to these groups.
Faktor-Faktor yang Berhubungan dengan Kejadian Kecelakaan Kerja di Laboratorium Pendidikan
Authors: Cahyaningrum Dwi , Muktiana Sari Hanif Tegar , Iswandari Dini 
Published: December 2021

Laboratory occupational safety is an action to prevent the occurrence of accident in laboratory environment caused by design, system, process and activities in laboratory. Laboratory with all desain and activities have a potencial hazard of accident. This study aimed to know factors related with the incident of accident in education laboratory. This is a cross sectional study with quantitative approach. Primary data was collected using questionnaire to 30 student in the last semester. Data were analyzed using chi square test at significance level at 0,05. The result show that the most accident occurred in laboratory are contact with the hot object, exposed to chemical spills, and also asphyxiation. The results also show that there is no related between the application of standart operated procedure and the knowledge level of student with the incident of occupational accident, and there is a relation between the use of personal protective equipment with the incident of occupational accident in education laboratory