bluuebunny/crossref_metadata_2025 huggingface dataset:
Reproductive justice in the time of COVID-19: a systematic review of the indirect impacts of COVID-19 on sexual and reproductive health
Authors: Mukherjee Trena I. , Khan Angubeen G. , Dasgupta Anindita , Samari Goleen
Published: December 2021

Objective

Despite gendered dimensions of COVID-19 becoming increasingly apparent, the impact of COVID-19 and other respiratory epidemics on women and girls’ sexual and reproductive health (SRH) have yet to be synthesized. This review uses a reproductive justice framework to systematically review empirical evidence of the indirect impacts of respiratory epidemics on SRH.

Methods

We searched MEDLINE and CINAHL for original, peer-reviewed articles related to respiratory epidemics and women and girls’ SRH through May 31, 2021. Studies focusing on various SRH outcomes were included, however those exclusively examining pregnancy, perinatal-related outcomes, and gender-based violence were excluded due to previously published systematic reviews on these topics. The review consisted of title and abstract screening, full-text screening, and data abstraction.

Results

Twenty-four studies met all eligibility criteria. These studies emphasized that COVID-19 resulted in service disruptions that effected access to abortion, contraceptives, HIV/STI testing, and changes in sexual behaviors, menstruation, and pregnancy intentions.

Conclusions

These findings highlight the need to enact policies that ensure equitable, timely access to quality SRH services for women and girls, despite quarantine and distancing policies. Research gaps include understanding how COVID-19 disruptions in SRH service provision, access and/or utilization have impacted underserved populations and those with intersectional identities, who faced SRH inequities notwithstanding an epidemic. More robust research is also needed to understand the indirect impact of COVID-19 and epidemic control measures on a wider range of SRH outcomes (e.g., menstrual disorders, fertility services, gynecologic oncology) in the long-term.
Emotions towards potential genetic offspring among oocyte donors: a cross-sectional study
Authors: Khosravi Sahar , Kazemi Ashraf , Ahmadi Seyyed Mehdi
Published: December 2021

Background

The presence of maternal emotions towards the offspring resulting from assisted reproductive techniques (ART) has been previously reported in oocyte donors. However, there is limited information about the presence of these emotions in oocyte donors during the ART process and before pregnancy. The aim of this study was to evaluate the emotions of oocyte donor women towards the potential genetic offspring and to compare them with women treated with ART by using own oocytes.

Methods

A cross-sectional study was conducted on 100 women who were divided into two groups of oocyte donors and those treated with ART and using autologous oocyte. At the time of oocyte retrieval. Using a validated questionnaire, the emotions toward potential offspring (EPO) resulting from ART and its three dimensions (including imagination, sense of ownership, and importance of treatment outcome) were measured and compared in two groups.

Results

Comparison of the EPO in the two groups showed that the emotions in all three dimensions were lower in oocyte donors than the other group (p < 0.001). Moreover, in oocyte donors, the mean score of the scale of the importance of treatment outcome dimension was higher than the other two scales (p < 0.001).

Conclusion

The results of the study showed that there is a significant emotion toward the potential offspring in oocyte donors. The presence of these emotions thus should be considered in formulating the ethical charter of ART by using oocyte donation.
Impact of using creative arts programming to support HIV treatment in adolescents and young adults in Eswatini
Authors: Ness Tara E. , Agrawal Vedika , Guffey Danielle , Small Amanda , Simelane Tandzile , Dlamini Sandile , Petrus Jaime , Lukhele Bhekumusa
Published: December 2021

Background

In 2018, approximately 1.6 million adolescents (aged 10–19) were living with HIV worldwide, with the highest HIV prevalence found in Eswatini. Adolescents and young adults living with HIV are a vulnerable population due to unique psychosocial challenges that come with having a stigmatizing disease. This group struggles more than other age-groups with medication adherence and requires novel approaches to supporting treatment, including peer-group encouragement, and self-expression.

Methods

We piloted a theater camp for a group of adolescents and young adults enrolled at our HIV clinic in Mbabane, Eswatini, to determine the impact of having an outlet for creative expression and peer support on treatment and feelings of stigma. Pre- and post-camp surveys were administered to the participants to assess perceived stigma and impact of the camp. The results were analyzed using a Wilcoxon-signed rank test.

Results

Twenty individuals (ages 12–23) living with HIV participated in the camp concurrently with standard treatment. 25% showed a substantial decrease in viral load within six months of completing the camp (> 0.1 log10 change) while only 10% showed a substantial increase. Those who completed the survey felt the camp helped them with confidence, teamwork, and friendships. A comparison of pre- and post- surveys showed an overall decrease in personalized stigma. Quotes from participants reinforced these results.

Conclusions

Adolescents and young adults living with HIV are an important population for further program development. Our study showed creative arts programming has beneficial psychosocial effects, aids in community building, and potentially enhances the effectiveness of medical treatment. Further programs and studies should continue to investigate creative arts as an avenue for self-expression and community building among vulnerable populations.
Hyperuricemia as a prognostic marker for long-term outcomes in patients with myocardial infarction with nonobstructive coronary arteries
Authors: Ma Wenjian , Gao Side , Huang Sizhuang , Yuan Jiansong , Yu Mengyue
Published: December 2021

Background

Hyperuricemia (HUA) has been proved as a predictor of worse outcomes in patients with coronary artery disease. Here, we investigated the prognostic value of HUA in a distinct population with myocardial infarction with nonobstructive coronary arteries (MINOCA).

Methods

A total of 1179 MINOCA patients were enrolled and divided into HUA and non-HUA groups. HUA was defined as a serum uric acid level ≥ 420 μmol/L in men or ≥ 357 μmol/L in women. The primary study endpoint was a composite of major adverse cardiovascular events (MACE), including all-cause death, nonfatal MI, nonfatal stroke, revascularization, and hospitalization for unstable angina or heart failure. Kaplan–Meier, Cox regression, and receiver-operating characteristic analyses were performed.

Results

Patients with HUA (prevalence of 23.5%) had a significantly higher incidence of MACE (18.7% vs. 12.8%; p = 0.015) than patients without during the median follow-up of 41.7 months. HUA was closely associated with an increased risk of MACE even after multivariable adjustment (hazard ratio 1.498, 95% confidence interval: 1.080 to 2.077; p = 0.016). HUA remained a robust risk factor of MACE after propensity score matching analysis. Moreover, HUA showed an area under the curve (AUC) of 0.59 for predicting MACE. Incorporation of HUA to the thrombolysis in myocardial infarction (TIMI) score yielded a significant improvement in discrimination for MACE.

Conclusions

HUA was independently associated with poor prognosis after MINOCA. Routine assessment of HUA may facilitate risk stratification in this specific population.
Association between clinical symptoms and apolipoprotein A1 or apolipoprotein B levels is regulated by apolipoprotein E variant rs429358 in patients with chronic schizophrenia
Authors: Rao Wenwang , Meng Xiangfei , Li Keqing , Zhang Yunshu , Zhang Xiang Yang
Published: December 2021

Background

The apolipoprotein E (ApoE) gene polymorphisms are correlated with blood lipid levels and several neuropsychiatric symptoms. Therefore, this study aimed to examine whether the ApoE rs429358 affected the development and clinical symptoms of schizophrenia and to explore the relationship between apolipoproteins levels and clinical symptoms.

Methods

The ApoE rs429358 was genotyped using a case–control design. The Positive and Negative Syndrome Scale (PANSS) was employed to evaluate the psychopathology of all patients.

Results

A total of 637 patients with schizophrenia and 467 healthy controls were recruited. We found no significant differences in the genotype and allele distribution between the patient and control groups. A significant correlation between PANSS negative symptoms and ApoA1 levels (p = 0.048) or ApoB levels (p = 0.001) was found in patients with schizophrenia, which was also confirmed by linear regression analyses (p = 0.048 vs. p = 0.001). Interestingly, only in the T homozygote group, ApoA1 and ApoB levels were predictors of the PANSS negative symptom score (p = 0.008 vs. p = 0.012), while in the C allele carrier group, no correlation was observed.

Conclusions

This study found that the levels of ApoA1 and ApoB were negatively associated with negative symptoms of patients with schizophrenia. Furthermore, the association between ApoA1 or ApoB levels and psychopathology of schizophrenia was regulated by ApoE rs429358.
Complementarity of Raman and Infrared spectroscopy for rapid characterization of fucoidan extracts
Authors: Ptak Signe H. , Sanchez Lee , Fretté Xavier , Kurouski Dmitry
Published: December 2021

Background

Fucoidans are sulfated polysaccharides from the cell-wall of brown algae. They have a wide range of applications in medicine, including regenerative medicine, ophthalmology, cancer, and autoimmune disease. Biological activity of fucoidans directly depends on their structure, which remains poorly understood. This is primarily because the polymeric nature of these molecules limits the use of nuclear magnetic resonance and mass spectrometry, classical tools of structural biology for their structural characterization. Raman and Infrared spectroscopies are non-invasive and non-destructive techniques that can be used to probe the structural organization of biological specimens. In this study, we investigate the potential of Raman and Infrared spectroscopy for structural analysis of several fucoidan extracts.

Results

Our results show that Infrared and Raman provide different but complimentary information about the structure of crude extracts of fucoidans, revealing the presence of minor impurities from co-extractants. We also found that at high extraction temperatures acidic conditions limit formation of melanoidins, while also yielding relatively high sulfate ester fucoidan. However, at high temperatures, water extraction may potentially result in formation of advanced glycation end products. Their presence could be problematic for fucoidan extracts intended for medicinal use, as advanced glycation end products have been linked to endocrine interruption mechanisms in vivo by crosslinking to and permanently altering extracellular matrix proteins.

Conclusion

Raman and Infrared can be used as complementary tools for rapid screening of crude fucoidan extracts, which can be a valuable tool for assessing impurities that remain after extraction.
Glioblastoma radiotherapy using Intensity modulated Radiotherapy (IMRT) or proton Radiotherapy—GRIPS Trial (Glioblastoma Radiotherapy via IMRT or Proton BeamS): a study protocol for a multicenter, prospective, open-label, randomized, two-arm, phase III study
Authors: König Laila , Jäkel Cornelia , von Knebel Doeberitz Nikolaus , Kieser Meinhard , Eberle Fabian , Münter Marc , Debus Jürgen , Herfarth Klaus
Published: December 2021

Background

Radiation therapy is an integral part of the multimodal primary therapy of glioblastomas. As the overall prognosis in this tumor entity remains unfavorable, current research is focused on additional drug therapies, which are often accompanied by increases in toxicity. By using proton beams instead of photon beams, it is possible to protect large parts of the brain which are not affected by the tumor more effectively. An initial retrospective matched-pair analysis showed that this theoretical physical benefit is also clinically associated with a reduction in toxicity during therapy and in the first few months thereafter.

Methods/design

The GRIPS trial is a multicenter, prospective, open-label, randomized, two-arm, phase III study using either intensity modulated photon radiation techniques (standard arm) or proton beam radiotherapy (experimental arm). Additionally, patients are stratified according to "fractionation scheme" (normofractionated/hypofractionated), "subventricular zone involvement" (yes/no) and concurrent chemotherapy (yes/no) and the planned case number is 326 patients.

Radiation therapy is performed with a dose of 30 × 2 Gy(RBE) or 33 × 1.8 Gy(RBE), or for patients treated according to the hypofractionation protocol with 15 × 2.67 Gy(RBE). A possible administration of additional chemotherapy (concurrent or adjuvant) or tumor treating fields is applied in dosage and frequency according to the therapy standard outside of this study. The primary endpoint is the cumulative rate of toxicity CTC grade 2 and higher in the first 4 months. Secondary endpoints include overall survival, progression-free survival, quality of life, and neurocognition.

Discussion

Aim of the GRIPS study is to prospectively assess whether the theoretical physical advantage of proton beam radiotherapy will translate into a clinical reduction of toxicity during and in the first months after therapy.

Trial registration

ClinicalTrials (NCT): NCT04752280.
Comparison of intra-articular administration of adenosine, lidocaine and magnesium solution and tranexamic acid for alleviating postoperative inflammation and joint fibrosis in an experimental model of knee arthroplasty
Authors: Morris Jodie L. , Letson Hayley L. , McEwen Peter , Biros Erik , Dlaska Constantin , Hazratwala Kaushik , Wilkinson Matthew , Dobson Geoffrey P.
Published: December 2021

Background

Dysregulated inflammatory responses are implicated in the pathogenesis of joint stiffness and arthrofibrosis following total knee arthroplasty (TKA). The purpose of this study was to compare the effects of intra-articular (IA) administration of tranexamic acid (TXA), an anti-fibrinolytic commonly used in TKA, and ALM chondroprotective solution on postoperative inflammation and joint tissue healing in a rat model of knee implant surgery.

Methods

Male Sprague–Dawley rats (n = 24) were randomly divided into TXA or ALM treatment groups. The right knee of each rat was implanted with titanium (femur) and polyethylene (tibia) implants. An IA bolus (0.1 ml) of TXA or ALM was administered after implantation and capsule closure, and before skin closure. Postoperative coagulopathy, haematology and systemic inflammatory changes were assessed. Inflammatory and fibrotic markers were assessed in joint tissue, 28 days after surgery.

Results

Haemostasis was comparable in animals treated with TXA or ALM after knee implant surgery. In contrast to ALM-treated animals, systemic inflammatory markers remained elevated at day 5 (IL-6, IL-12, IL-10, platelet count) and day 28 (IL-1β, IL-10) following surgery in TXA-treated animals. At day 28 following surgery, the extension range of motion of operated knees was 1.7-fold higher for ALM-treated animals compared to the TXA group. Key inflammatory mediators (NF-κB, IL-12, IL-2), immune cell infiltration (CD68+cells) and markers of fibrosis (α-SMA, TGF-β) were also lower in capsular tissue of ALM-treated knees at day 28.

Conclusion

Data suggest that IA administration of ALM is superior to TXA for reducing postoperative systemic and joint inflammation and promoting restoration of healthy joint tissue architecture in a rat model of TKA. Further studies are warranted to assess the clinical translational potential of ALM IA solution to improve patient outcomes following arthroplasty.
Management of instability after primary total knee arthroplasty: an evidence-based review
Authors: Al-Jabri Talal , Brivio Angela , Maffulli Nicola , Barrett David
Published: December 2021

Background

Instability is one of the most common reasons for revision after a total knee replacement. It accounts for 17.4% of all single-stage revision procedures performed in the UK National Joint Registry. Through a careful patient evaluation, physical assessment and review of investigations one can identify the likely type of instability.

Aims

To critically examine the different types of instability, their presentation and evidence-based management options.

Method

A comprehensive literature search was conducted to identify articles relevant to the aetiology and management of instability in total knee replacements.

Results

Instability should be categorised as isolated or global and then, as flexion, mid-flexion, extension or recurvatum types. By identifying the aetiology of instability one can correctly restore balance and stability.

Conclusion

With careful judgement and meticulous surgical planning, instability can be addressed and revision surgery can provide patients with successful outcomes.
The relationship of C-reactive protein/interleukin-6 concentrations between serum and synovial fluid in the diagnosis of periprosthetic joint infection
Authors: Yu Bao-Zhan , Li Rui , Li Xiang , Chai Wei , Zhou Yong-Gang , Chen Ji-Ying
Published: December 2021

Background

The relationship of C-reactive protein (CRP)/interleukin-6 (IL-6) concentrations between serum and synovial fluid and whether synovial CRP/IL-6 testing in addition to serum CRP/IL-6 testing would result in a benefit in the diagnosis of periprosthetic joint infection (PJI) deserves to be investigated.

Methods

From June 2016 to July 2019, 139 patients were included in the study. Synovial CRP and IL-6 were tested by ELISA. The serum CRP and IL-6 were obtained from medical records. The definition of PJI was based on the modified Musculoskeletal Infection Society (MSIS) criteria. The relationship of serum and synovial CRP and IL-6 and the value of each index in the diagnosis of PJI were evaluated.

Results

The receiver operating characteristic (ROC) curves showed that synovial IL-6 had the highest area under the curve (AUC) at 0.935, which was followed by synovial CRP, serum IL-6 and serum CRP 0.861, 0.847 and 0.821, respectively. When combining serum CRP and synovial CRP to diagnose PJI, the AUC was 0.849, which was slightly higher than the result obtained when using serum CRP alone. In contrast, when combining serum IL-6 and synovial IL-6 to diagnose PJI, the AUC increased to 0.940, which was significantly higher than that obtained using serum IL-6 alone.

Conclusion

The synovial IL-6 has the highest diagnostic accuracy for PJI. However, inferring the level of CRP/IL-6 in the synovial fluid from the serum level of CRP/IL-6 was not feasible. Synovial CRP testing did not offer an advantage when combined with an existing serum CRP result to diagnose PJI, while additional synovial IL-6 was worthy of testing even if there was an existing serum IL-6 result.
Mental health diagnoses in adults with phenylketonuria: a retrospective systematic audit in a large UK single centre
Authors: Altman George , Hussain Kamran , Green Diane , Strauss Boyd J. G. , Wilcox Gisela
Published: December 2021

Background

Recently published European Society for Phenylketonuria (ESPKU) guidelines have recommended a lifelong diet with phenylalanine (Phe) control ≤ 600 μmol/L for phenylketonuria (PKU) patients. This study aimed to identify whether PKU adult patients are at a higher risk of mental health diagnoses if their 2-year average Phe level is higher than the ESPKU European guidelines. Published studies identified by a literature review showed that related studies have been published in American and European PKU study populations but not in the United Kingdom (UK) study populations. Previous studies also involved a smaller number of participants due to this being a rare disease.

Results

We undertook a retrospective audit at a single large PKU centre in the UK. 244 adult PKU patients at the centre were included, 220 of which had a recorded Phe level. Approximately 75% of the patients in this study did not meet the ESPKU European guidelines for Phe control. A systematic search of the electronic patient record was undertaken looking for mental health diagnoses. Compared to two-year average Phe levels ≤ 600 μmol/L, PKU adult patients with two-year average Phe levels > 600 μmol/L were more likely to have diagnoses of low mood, depression, anxiety, or mood swings, but only low mood reached statistical significance (p < 0.05).

Conclusions

PKU patients with two-year average Phenylalanine levels greater than ESPKU guidelines may be at greater risk of mental health diagnoses and symptoms. Many of these adult PKU patients will be lost to follow-up, and therefore may be receiving treatment for mental health conditions in the community. Multicentre UK studies and international collaborations are required to overcome low participant numbers in the study of this rare disease.
Effects of socio-economic factors on research over systemic sclerosis: an analysis based on long time series of bibliometric data
Authors: Guo Wei , Zhou Zeyu , Liang Yinhe , Xu Chuanhui , Zeng Lin , Dong Zhiyong , Mu Rong
Published: December 2021

Background

Systemic sclerosis (SSc) is a rare detrimental disease warranting global research efforts. Evaluating how socio-economic factors impact country research output on SSc could help to identify solutions advancing research.

Methods

Publication production on SSc during 1969–2018 and data for structural and policy factors for WHO member countries were collected from public sources. Associations between SSc research output and country-level factors were investigated through panel regression. Difference-in-differences analysis further assessed the causal effects of rare disease legislation.

Results

SSc publications demonstrated exponential growth (r = 0.9410, as against anr = 0.8845 after linear adjustment), but were concentrated in high-income countries (HICs). Ten countries, nine of which were HICs, published 12,261 (77.5%) SSc publications but another 87 countries produced none. Gross domestic products (GDP), population and expenditure on research and development were positively associated with SSc publications (p < 0.001). Higher health expenditure was only found to be associated with increased SSc publications in HICs (p < 0.001). Rare disease legislation increased annual publication production by 62.8% (95% CI 0.390–0.867;p < 0.001) averagely. In middle-income countries (MICs), the effect was especially swift and lasting. No significant impact was found with GDP per capita, female percentage, and political indicators.

Conclusions

SSc research output increased over time with substantial country disparities. Effective health policies facilitating research should be expanded especially among MICs to accelerate research advancement.
Challenges and opportunities for infection prevention and control in hospitals in conflict-affected settings: a qualitative study
Authors: Lowe Hattie , Woodd Susannah , Lange Isabelle L. , Janjanin Sanja , Barnet Julie , Graham Wendy
Published: December 2021

Background

Healthcare associated infections (HAIs) are the most frequent adverse outcome in healthcare delivery worldwide. In conflict-affected settings HAIs, in particular surgical site infections, are prevalent. Effective infection prevention and control (IPC) is crucial to ending avoidable HAIs and an integral part of safe, effective, high quality health service delivery. However, armed conflict and widespread violence can negatively affect the quality of health care through workforce shortages, supply chain disruptions and attacks on health facilities and staff. To improve IPC in these settings it is necessary to understand the specific barriers and facilitators experienced locally.

Methods

In January and February of 2020, we conducted semi-structured interviews with hospital staff working for the International Committee of the Red Cross across eight conflict-affected countries (Central African Republic, South Sudan, Democratic Republic of the Congo, Mali, Nigeria, Lebanon, Yemen and Afghanistan). We explored barriers and facilitators to IPC, as well as the direct impact of conflict on the hospital and its’ IPC programme. Data was analysed thematically.

Results

We found that inadequate hospital infrastructure, resource and workforce shortages, education of staff, inadequate in-service IPC training and supervision and large visitor numbers are barriers to IPC in hospitals in this study, similar to barriers seen in other resource-limited settings. High patient numbers, supply chain disruptions, high infection rates and attacks on healthcare infrastructures, all as a direct result of conflict, exacerbated existing challenges and imposed an additional burden on hospitals and their IPC programmes. We also found examples of local strategies for improving IPC in the face of limited resources, including departmental IPC champions and illustrated guidelines for in-service training.

Conclusions

Hospitals included in this study demonstrated how they overcame certain challenges in the face of limited resources and funding. These strategies present opportunities for learning and knowledge exchange across contexts, particularly in the face of the current global coronavirus pandemic. The findings are increasingly relevant today as they provide evidence of the fragility of IPC programmes in these settings. More research is required on tailoring IPC programmes so that they can be feasible and sustainable in unstable settings.
HIF-1α switches the functionality of TGF-β signaling via changing the partners of smads to drive glucose metabolic reprogramming in non-small cell lung cancer
Authors: Huang Yiwei , Chen Zhencong , Lu Tao , Bi Guoshu , Li Ming , Liang Jiaqi , Hu Zhengyang , Zheng Yuansheng , Yin Jiacheng , Xi Junjie , Lin Zongwu , Zhan Cheng , Jiang Wei , Wang Qun , Tan Lijie
Published: December 2021

Background

Most cancer cells have fundamentally different metabolic characteristics, particularly much higher glycolysis rates than normal tissues, which support the increased demand for biosynthesis and promote tumor progression. We found that transforming growth factor (TGF)-β plays a dual function in regulating glycolysis and cell proliferation in non-small cell lung cancer.

Methods

We used the PET/MRI imaging system to observe the glucose metabolism of subcutaneous tumors in nude mice. Energy metabolism of non-small cell lung cancer cell lines detected by the Seahorse XFe96 cell outflow analyzer. Co-immunoprecipitation assays were used to detect the binding of Smads and HIF-1α. Western blotting and qRT-PCR were used to detect the regulatory effects of TGF-β and HIF-1α on c-MYC, PKM1/2, and cell cycle-related genes.

Results

We discovered that TGF-β could inhibit glycolysis under normoxia while significantly promoting tumor cells’ glycolysis under hypoxia in vitro and in vivo. The binding of hypoxia-inducible factor (HIF)-1α to the MH2 domain of phosphorylated Smad3 switched TGF-β function to glycolysis by changing Smad partners under hypoxia. The Smad-p107-E2F4/5 complex that initially inhibited c-Myc expression was transformed into a Smad-HIF-1α complex that promoted the expression of c-Myc. The increased expression of c-Myc promoted alternative splicing of PKM to PKM2, resulting in the metabolic reprogramming of tumor cells. In addition, the TGF-β/Smad signal lost its effect on cell cycle regulatory protein p15/p21. Furthermore, high expression of c-Myc inhibited p15/p21 and promoted the proliferation of tumor cells under hypoxia.

Conclusions

Our results indicated that HIF-1α functions as a critical factor in the dual role of TGF-β in tumor cells, and may be used as a biomarker or therapeutic target for TGF-β mediated cancer progression.
New anatomical reference systems for the bones of the foot and ankle complex: definitions and exploitation on clinical conditions
Authors: Conconi Michele , Pompili Alessandro , Sancisi Nicola , Leardini Alberto , Durante Stefano , Belvedere Claudio
Published: December 2021

Background

A complete definition of anatomical reference systems (ARS) for all bones of the foot and ankle complex is lacking. Using a morphological approach, we propose new ARS for these bones with the aim of being highly repeatable, consistent among individuals, clinically interpretable, and also suited for a sound kinematic description.

Methods

Three specimens from healthy donors and three patients with flat feet were scanned in weight‐bearing CT. The foot bones were segmented and ARS defined according to the proposed approach.

To assess repeatability, intra class coefficients (ICC) were computed both intra‐ and inter‐operator.

Consistency was evaluated as the mean of the standard deviations of the ARS position and orientation, both within normal and flat feet.

Clinical interpretability was evaluated by providing a quantification of the curvature variation in the medial‐longitudinal and transverse arches and computing the Djiann‐Annonier angle for normal and flat feet from these new ARS axes.

To test the capability to also provide a sound description of the foot kinematics, the alignment between mean helical axes (MHA) and ARS axes was quantified.

Results

ICC was 0.99 both inter‐ and intra‐operator.

Rotational consistency was 4.7 ± 3.5 ° and 6.2 ± 4.4° for the normal and flat feet, respectively; translational consistency was 4.4 ± 4.0 mm and 5.4 ± 2.9 mm for the normal and flat feet, respectively. In both these cases, the consistency was better than what was achieved by using principal axes of inertia.

Curvature variation in the arches were well described and the measurements of the Djiann‐Annoier angles from both normal and flat feet matched corresponding clinical observations.

The angle between tibio‐talar MHA and ARS mediolateral axis in the talus was 12.3 ± 6.0, while the angle between talo‐calcaneal MHA and ARS anteroposterior axis in the calcaneus was 17.2 ± 5.6, suggesting good capability to represent joint kinematics.

Conclusions

The proposed ARS definitions are robust and provide a solid base for the 3‐dimensional description of posture and motion of the foot and ankle complex from medical imaging.
Exploring population pharmacokinetic models in patients treated with vancomycin during continuous venovenous haemodiafiltration (CVVHDF)
Authors: Kirwan Marcus , Munshi Reema , O’Keeffe Hannah , Judge Conor , Coyle Mary , Deasy Evelyn , Kelly Yvelynne P. , Lavin Peter J. , Donnelly Maria , D’Arcy Deirdre M.
Published: December 2021

Background

Therapeutic antibiotic dose monitoring can be particularly challenging in septic patients requiring renal replacement therapy. Our aim was to conduct an exploratory population pharmacokinetic (PK) analysis on PK of vancomycin following intermittent infusion in critically ill patients receiving continuous venovenous haemodiafiltration (CVVHDF); focussing on the influence of dialysis-related covariates.

Methods

This was a retrospective single-centre tertiary level intensive care unit (ICU) study, which included patients treated concurrently with vancomycin and CVVHDF between January 2015 and July 2016. We extracted clinical, laboratory and dialysis data from the electronic healthcare record (EHR), using strict inclusion criteria. A population PK analysis was conducted with a one-compartment model using the PMetrics population PK modelling package. A base structural model was developed, with further analyses including clinical and dialysis-related data to improve model prediction through covariate inclusion. The final selected model simulated patient concentrations using probability of target attainment (PTA) plots to investigate the probability of different dosing regimens achieving target therapeutic concentrations.

Results

A total of 106 vancomycin dosing intervals (155 levels) in 24 patients were examined. An acceptable 1-compartment base model was produced (Plots of observed vs. population predicted concentrations (Obs–Pred) R2 = 0.78). No continuous covariates explored resulted in a clear improvement over the base model. Inclusion of anticoagulation modality and vasopressor use as categorical covariates resulted in similar PK parameter estimates, with a trend towards lower parameter estimate variability when using regional citrate anti-coagulation or without vasopressor use. Simulations using PTA plots suggested that a 2 g loading dose followed by 750 mg 12 hourly as maintenance dose, commencing 12 h after loading, is required to achieve adequate early target trough concentrations of at least 15 mg/L.

Conclusions

PTA simulations suggest that acceptable trough vancomycin concentrations can be achieved early in treatment with a 2 g loading dose and maintenance dose of 750 mg 12 hourly for critically ill patients on CVVHDF.
Chronos: a cell population dynamics model of CRISPR experiments that improves inference of gene fitness effects
Authors: Dempster Joshua M. , Boyle Isabella , Vazquez Francisca , Root David E. , Boehm Jesse S. , Hahn William C. , Tsherniak Aviad , McFarland James M.
Published: December 2021

CRISPR loss of function screens are powerful tools to interrogate biology but exhibit a number of biases and artifacts that can confound the results. Here, we introduce Chronos, an algorithm for inferring gene knockout fitness effects based on an explicit model of cell proliferation dynamics after CRISPR gene knockout. We test Chronos on two pan-cancer CRISPR datasets and one longitudinal CRISPR screen. Chronos generally outperforms competitors in separation of controls and strength of biomarker associations, particularly when longitudinal data is available. Additionally, Chronos exhibits the lowest copy number and screen quality bias of evaluated methods. Chronos is available at https://github.com/broadinstitute/chronos.
The economics of organellar gene loss and endosymbiotic gene transfer
Authors: Kelly Steven
Published: December 2021

Background

The endosymbiosis of the bacterial progenitors of the mitochondrion and the chloroplast are landmark events in the evolution of life on Earth. While both organelles have retained substantial proteomic and biochemical complexity, this complexity is not reflected in the content of their genomes. Instead, the organellar genomes encode fewer than 5% of the genes found in living relatives of their ancestors. While many of the 95% of missing organellar genes have been discarded, others have been transferred to the host nuclear genome through a process known as endosymbiotic gene transfer.

Results

Here, we demonstrate that the difference in the per-cell copy number of the organellar and nuclear genomes presents an energetic incentive to the cell to either delete organellar genes or transfer them to the nuclear genome. We show that, for the majority of transferred organellar genes, the energy saved by nuclear transfer exceeds the costs incurred from importing the encoded protein into the organelle where it can provide its function. Finally, we show that the net energy saved by endosymbiotic gene transfer can constitute an appreciable proportion of total cellular energy budgets and is therefore sufficient to impart a selectable advantage to the cell.

Conclusion

Thus, reduced cellular cost and improved energy efficiency likely played a role in the reductive evolution of mitochondrial and chloroplast genomes and the transfer of organellar genes to the nuclear genome.
Quantitative-enhancer-FACS-seq (QeFS) reveals epistatic interactions among motifs within transcriptional enhancers in developing Drosophila tissue
Authors: Waters Colin T. , Gisselbrecht Stephen S. , Sytnikova Yuliya A. , Cafarelli Tiziana M. , Hill David E. , Bulyk Martha L.
Published: December 2021

Understanding the contributions of transcription factor DNA binding sites to transcriptional enhancers is a significant challenge. We developed Quantitative enhancer-FACS-Seq for highly parallel quantification of enhancer activities from a genomically integrated reporter inDrosophila melanogasterembryos. We investigate the contributions of the DNA binding motifs of four poorly characterized TFs to the activities of twelve embryonic mesodermal enhancers. We measure quantitative changes in enhancer activity and discover a range of epistatic interactions among the motifs, both synergistic and alleviating. We find that understanding the regulatory consequences of TF binding motifs requires that they be investigated in combination across enhancer contexts.
INTEnsive care bundle with blood pressure reduction in acute cerebral hemorrhage trial (INTERACT3): study protocol for a pragmatic stepped-wedge cluster-randomized controlled trial
Authors: Song Lili , Hu Xin , Ma Lu , Chen Xiaoying , Ouyang Menglu , Billot Laurent , Li Qiang , Muñoz-Venturelli Paula , Abanto Carlos , Pontes-Neto Octavio Marques , Antonio Arauz , Wasay Mohammad , Silva Asita de , Thang Nguyen Huy , Pandian Jeyaraj Durai , Wahab Kolawole Wasiu , You Chao , Anderson Craig S. ,   for the INTERACT3 investigators
Published: December 2021

Background

Early intensive blood pressure (BP) lowering remains the most promising treatment for acute intracerebral hemorrhage (ICH), despite discordant results between clinical trials and potential variation in the treatment effects by approach to control BP. As the third in a series of clinical trials on this topic, the INTEnsive care bundle with blood pressure Reduction in Acute Cerebral hemorrhage Trial (INTERACT3) aims to determine the effectiveness of a goal-directed care bundle protocol of early physiological control (intensive BP lowering, glycemic control, and pyrexia treatment) and reversal of anticoagulation, in acute ICH.

Methods

INTERACT3 is a pragmatic, international, multicenter, stepped-wedge (4 phases/3 steps), cluster-randomized controlled trial to determine the effectiveness of a multifaceted care package in adult (age ≥ 18 years) patients (target 8360) with acute ICH (< 6 h of onset) recruited from 110 hospitals (average of 19 consecutive patients per phase) in low- and middle-income countries. After a control phase, each hospital implements the intervention (intensive BP lowering, target systolic < 140 mmHg; glucose control, target 6.1–7.8 mmol/L and 7.8–10.0 mmol/L in those without and with diabetes mellitus, respectively; anti-pyrexia treatment to target body temperature ≤ 37.5 °C; and reversal of anticoagulation, target international normalized ratio < 1.5 within 1 h). Information will be obtained on demographic and baseline clinical characteristics, in-hospital management, and 7-day outcomes. Central trained blinded assessors will conduct telephone interviews to assess physical function and health-related quality of life at 6 months. The primary outcome is the modified Rankin scale (mRS) at 6 months analyzed using ordinal logistic regression. The sample size of 8360 subjects provides 90% power (α = 0.05) to detect a 5.6% absolute improvement (shift) in the primary outcome of the intervention versus control standard care, with various assumptions.

Discussion

As the largest clinical trial in acute ICH, INTERACT3 is on schedule to provide an assessment of the effectiveness of a widely applicable goal-directed care bundle for a serious condition in which a clearly proven treatment has yet to be established.

Trial registration

ClinicalTrials.gov NCT03209258. Registered on 1 July 2017. Chinese Trial Registry ChiCTR-IOC-17011787. Registered on 28 June 2017
Eccentric-only versus concentric-only resistance training effects on biochemical and physiological parameters in patients with type 2 diabetes
Authors: Kudiarasu Christine , Rohadhia Wafina , Katsura Yoshihiro , Koeda Tomoko , Singh Favil , Nosaka Kazunori
Published: December 2021

Background

The benefits of resistance training for patients with type 2 diabetes (T2D) are well documented; however, the effects of exercise with different muscle contraction types such as eccentric versus concentric contractions on physiological outcomes for this population are not clear. This study compared eccentric-only (ECC) and concentric-only resistance training (CON) to test the hypothesis that ECC would be superior to CON to improve insulin sensitivity, lipid profile, body composition, muscle strength and physical function of patients with T2D.

Methods

Adults with T2D (50–79 years) were allocated to the ECC (n = 9) or CON group (n = 9). Resistance exercises (chest press, lateral pulldown, bicep curl, triceps extension, leg extension, leg curl, calf raise, abdominal crunch) consisting of 2–3 sets of 10 eccentric-only (5 s) or concentric-only contractions (1–2 s) was performed twice a week for 12 weeks. Changes in blood biomarkers, body composition, muscle strength and physical function from pre- to post-intervention were compared between groups.

Results

Overall rating of perceived exertion (RPE, 1–10 Borg scale) was lower (p < 0.05) for ECC (2.9 ± 1.2) than CON (5.4 ± 1.1). No significant changes in blood biomarkers were found for both groups. Lean mass increased [effect size (ES) = 0.148, ECC 3.2 ± 6.9%; CON 3.6 ± 2.3%], and fat mass decreased (ES = 0.545, ECC − 6.1 ± 12.4%; CON − 7.1 ± 16.4%) (p < 0.05) similarly. One-repetition maximal strength of each exercise increased (p < 0.05) for both ECC (12–37%) and CON (27–68%). Both groups improved (p < 0.05) 6-min walk distance (ES = 0.083, ECC 12.2 ± 2.3%; CON 12.5 ± 15.3%) and chair rise time (ES = 0.463, ECC − 13.4 ± 25.4%; CON − 20.0 ± 53.3%) but only ECC improved (p < 0.05) the timed up-and-go test (− 11.3 ± 13.6%, ES 0.014). No significant changes in balance tests were found for both groups.

Conclusion

These results did not fully support the hypothesis but showed that ECC was as effective as CON to improve body composition, muscle strength, and physical function with lesser RPE. Future studies should investigate whether larger differences between ECC and CON are evident when increasing the exercise frequency and matching the intensities of the two-exercise protocols.

Trial registration ACTRN12621001026819 (retrospectively registered on 5th Aug 2021).
Data on the Facebook marketing strategies used by fast-food chains in four Latin American countries during the COVID-19 lockdowns
Authors: Rozas Lucila , Castronuovo Luciana , Busse Peter , Mus Sophia , Barnoya Joaquín , Garrón Alejandra , Tiscornia María Victoria , Guanieri Leila
Published: December 2021

Objectives

During the COVID-19 pandemic, most countries implemented lockdowns that motivated changes in the dietary patterns, physical activity, and body mass index (BMI) of consumers worldwide, as well as the emergence of new food marketing strategies in social media. We sought to design and validate a methodology for monitoring and evaluating the Facebook marketing strategies of multinational fast-food chains in response to the COVID-19 pandemic.

Data description

We developed three datasets. First, a dataset with the Uniform Resource Locators (URLs) of 1015 Facebook posts of five fast-food chains present in Argentina, Bolivia, Guatemala, and Peru. Second, a dataset of 106 content-analyzed posts we used in a pilot to determine intercoder reliability using statistical tests. Third, a dataset of a final sample of the 1015 content-analyzed posts that we used to determine the variables most frequently used. Following a mixed-methods approach, we developed 29 variables that recorded general information, as well as the marketing strategies we identified in the posts, including 14 COVID-19 specific variables. These data should help to monitor the social media marketing strategies that fast-food chains have introduced during the COVID-19 lockdowns, thus providing initial evidence about how they could be contributing to an unhealthy food environment.
Impact of potential modifications to Alzheimer’s disease clinical trials in response to disruption by COVID-19: a simulation study
Authors: Schneider Lon S. , Qiu Yuqi , Thomas Ronald G. , Evans Carol , Jacobs Diane M. , Jin Shelia , Kaye Jeffrey A. , LaCroix Andrea Z. , Messer Karen , Salmon David P. , Sano Mary , Schafer Kimberly , Feldman Howard H.
Published: December 2021

Background

The COVID-19 pandemic disrupted Alzheimer disease randomized clinical trials (RCTs), forcing investigators to make changes in the conduct of such trials while endeavoring to maintain their validity. Changing ongoing RCTs carries risks for biases and threats to validity. To understand the impact of exigent modifications due to COVID-19, we examined several scenarios in symptomatic and disease modification trials that could be made.

Methods

We identified both symptomatic and disease modification Alzheimer disease RCTs as exemplars of those that would be affected by the pandemic and considered the types of changes that sponsors could make to each. We modeled three scenarios for each of the types of trials using existing datasets, adjusting enrollment, follow-ups, and dropouts to examine the potential effects COVID-19-related changes. Simulations were performed that accounted for completion and dropout patterns using linear mixed effects models, modeling time as continuous and categorical. The statistical power of the scenarios was determined.

Results

Truncating both symptomatic and disease modification trials led to underpowered trials. By contrast, adapting the trials by extending the treatment period, temporarily stopping treatment, delaying outcomes assessments, and performing remote assessment allowed for increased statistical power nearly to the level originally planned.

Discussion

These analyses support the idea that disrupted trials under common scenarios are better continued and extended even in the face of dropouts, treatment disruptions, missing outcomes, and other exigencies and that adaptations can be made that maintain the trials’ validity. We suggest some adaptive methods to do this noting that some changes become under-powered to detect the original effect sizes and expected outcomes. These analyses provide insight to better plan trials that are resilient to unexpected changes to the medical, social, and political milieu.
Deep learning approach for automatic segmentation of ulna and radius in dual-energy X-ray imaging
Authors: Yang Fan , Weng Xin , Miao Yuehong , Wu Yuhui , Xie Hong , Lei Pinggui
Published: December 2021

Background

Segmentation of the ulna and radius is a crucial step for the measurement of bone mineral density (BMD) in dual-energy X-ray imaging in patients suspected of having osteoporosis.

Purpose

This work aimed to propose a deep learning approach for the accurate automatic segmentation of the ulna and radius in dual-energy X-ray imaging.

Methods and materials

We developed a deep learning model with residual block (Resblock) for the segmentation of the ulna and radius. Three hundred and sixty subjects were included in the study, and five-fold cross-validation was used to evaluate the performance of the proposed network. The Dice coefficient and Jaccard index were calculated to evaluate the results of segmentation in this study.

Results

The proposed network model had a better segmentation performance than the previous deep learning-based methods with respect to the automatic segmentation of the ulna and radius. The evaluation results suggested that the average Dice coefficients of the ulna and radius were 0.9835 and 0.9874, with average Jaccard indexes of 0.9680 and 0.9751, respectively.

Conclusion

The deep learning-based method developed in this study improved the segmentation performance of the ulna and radius in dual-energy X-ray imaging.