bluuebunny/crossref_metadata_2025 huggingface dataset:
The relationship between telework from home and employee health: a systematic review
Authors: Lunde Lars-Kristian , Fløvik Lise , Christensen Jan Olav , Johannessen Håkon A. , Finne Live Bakke , Jørgensen Ingrid Løken , Mohr Benedicte , Vleeshouwers Jolien
Published: January 2022

Background

Globalization and technological progress have made telework arrangements such as telework from home (TWFH) well-established in modern economies. TWFH was rapidly and widely implemented to reduce virus spread during the Coronavirus disease (COVID-19) pandemic, and will probably be widespread also post-pandemic. How such work arrangements affect employee health is largely unknown. Main objective of this review was to assess the evidence on the relationship between TWFH and employee health.

Methods

We conducted electronic searches in MEDLINE, Embase, Amed, PsycINFO, PubMed, and Scopus for peer-reviewed, original research with quantitative design published from January 2010 to February 2021. Our aim was to assess the evidence for associations between TWFH and health-related outcomes in employed office workers. Risk of bias in each study was evaluated by the Newcastle-Ottawa Scale and the collected body of evidence was evaluated using the the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.

Results

We included 14 relevant studies (22,919 participants) reporting on 28 outcomes, which were sorted into six outcome categories (general health, pain, well-being, stress, exhaustion & burnout, and satisfaction with overall life & leisure). Few studies, with many having suboptimal designs and/or other methodological issues, investigating a limited number of outcomes, resulted in the body of evidence for the detected outcome categories being GRADED either as low or very low.

Conclusions

The consisting evidence on the relationship between TWFH and employee health is scarce. The non-existence of studies on many relevant and important health outcomes indicates a vast knowledge gap that is crucial to fill when determining how to implement TWFH in the future working life.

Systematic review registration number

PROSPERO registration ID # CRD42021233796.
The many faces of diabetes. Is there a need for re-classification? A narrative review
Authors: Sakran Nasser , Graham Yitka , Pintar Tadeja , Yang Wah , Kassir Radwan , Willigendael Edith M. , Singhal Rishi , Kooreman Zoë E. , Ramnarain Dharmanand , Mahawar Kamal , Parmar Chetan , Madhok Brijesh , Pouwels Sjaak
Published: January 2022

The alarming rise in the worldwide prevalence of obesity and associated type 2 diabetes mellitus (T2DM) have reached epidemic portions. Diabetes in its many forms and T2DM have different physiological backgrounds and are difficult to classify. Bariatric surgery (BS) is considered the most effective treatment for obesity in terms of weight loss and comorbidity resolution, improves diabetes, and has been proven superior to medical management for the treatment of diabetes. The term metabolic surgery (MS) describes bariatric surgical procedures used primarily to treat T2DM and related metabolic conditions. MS is the most effective means of obtaining substantial and durable weight loss in individuals with obesity. Originally, BS was used as an alternative weight-loss therapy for patients with severe obesity, but clinical data revealed its metabolic benefits in patients with T2DM. MS is more effective than lifestyle or medical management in achieving glycaemic control, sustained weight loss, and reducing diabetes comorbidities. New guidelines for T2DM expand the use of MS to patients with a lower body mass index.

Evidence has shown that endocrine changes resulting from BS translate into metabolic benefits that improve the comorbid conditions associated with obesity, such as hypertension, dyslipidemia, and T2DM. Other changes include bacterial flora rearrangement, bile acids secretion, and adipose tissue effect.

This review aims to examine the physiological mechanisms in diabetes, risks for complications, the effects of bariatric and metabolic surgery and will shed light on whether diabetes should be reclassified.
Nucleus-cytoskeleton communication impacts on OCT4-chromatin interactions in embryonic stem cells
Authors: Romero Juan José , De Rossi María Cecilia , Oses Camila , Echegaray Camila Vázquez , Verneri Paula , Francia Marcos , Guberman Alejandra , Levi Valeria
Published: January 2022

Background

The cytoskeleton is a key component of the system responsible for transmitting mechanical cues from the cellular environment to the nucleus, where they trigger downstream responses. This communication is particularly relevant in embryonic stem (ES) cells since forces can regulate cell fate and guide developmental processes. However, little is known regarding cytoskeleton organization in ES cells, and thus, relevant aspects of nuclear-cytoskeletal interactions remain elusive.

Results

We explored the three-dimensional distribution of the cytoskeleton in live ES cells and show that these filaments affect the shape of the nucleus. Next, we evaluated if cytoskeletal components indirectly modulate the binding of the pluripotency transcription factor OCT4 to chromatin targets. We show that actin depolymerization triggers OCT4 binding to chromatin sites whereas vimentin disruption produces the opposite effect. In contrast to actin, vimentin contributes to the preservation of OCT4-chromatin interactions and, consequently, may have a pro-stemness role.

Conclusions

Our results suggest roles of components of the cytoskeleton in shaping the nucleus of ES cells, influencing the interactions of the transcription factor OCT4 with the chromatin and potentially affecting pluripotency and cell fate.
Effects of carrier solutions on the viability and efficacy of canine adipose-derived mesenchymal stem cells
Authors: Sultana Tania , Dayem Ahmed Abdal , Lee Soo Bin , Cho Ssang-Goo , Lee Jeong Ik
Published: January 2022

Background

Mesenchymal stem cells (MSCs) have favorable characteristics that render them a potent therapeutic tool. We tested the characteristics of MSCs after temporal storage in various carrier solutions, such as 0.9% saline (saline), 5% dextrose solution (DS), heparin in saline, and Hartmann’s solution, all of which are approved by the U.S. Food and Drug Administration (FDA). Phosphate-buffered saline, which does not have FDA approval, was also used as a carrier solution. We aimed to examine the effects of these solutions on the viability and characteristics of MSCs to evaluate their suitability and efficacy for the storage of canine adipose-derived MSCs (cADMSCs).

Results

We stored the cADMSCs in the test carrier solutions in a time-dependent manner (1, 6, and 12 h) at 4 °C, and analyzed cell confluency, viability, proliferation, self-renewability, and chondrogenic differentiation. Cell confluency was significantly higher in 5% DS and lower in phosphate-buffered saline at 12 h compared to other solutions. cADMSCs stored in saline for 12 h showed the highest viability rate. However, at 12 h, the proliferation rate of cADMSCs was significantly higher after storage in 5% DS and significantly lower after storage in saline, compared to the other solutions. cADMSCs stored in heparin in saline showed superior chondrogenic capacities at 12 h compared to other carrier solutions. The expression levels of the stemness markers, Nanog and Sox2, as well as those of the MSC surface markers, CD90 and CD105, were also affected over time.

Conclusion

Our results suggest that MSCs should be stored in saline, 5% DS, heparin in saline, or Hartmann’s solution at 4 °C, all of which have FDA approval (preferable storage conditions: less than 6 h and no longer than 12 h), rather than storing them in phosphate-buffered saline to ensure high viability and efficacy.
Horses’ rejection behaviour towards the presence of Senecio jacobaea L. in hay
Authors: Sroka Louisa , Müller Clara , Hass Marie-Lena , These Anja , Aboling Sabine , Vervuert Ingrid
Published: January 2022

Background

Senecio jacobaea contains pyrrolizidine alkaloids that can induce severe hepatic intoxication in horses, either acute when ingested in high amounts or chronic when consumed over a long period. The aim of this study was to determine horses’ rejection behaviour towards the presence of Senecio jacobaea in hay when fed ad libitum. We hypothesized that adult horses can sort Senecio jacobaea out of the contaminated hay when hay is fed ad libitum. Six warmblood geldings with a mean (±SD) age of 15 ± 2 years were included. In a randomized study, Senecio jacobaea contaminated hay (5% or 10% contamination level) was provided at several timepoints over the day for 1 hour to six. Hay was provided ad libitum for the rest of the day. The horses’ rejection behaviour towards Senecio jacobaea was observed. If a horse ingested two Senecio jacobaea plants twice at different timepoints, then the horse was excluded from the experiment.

Results

Two out of six horses had to be excluded from the study after three out of 12 observation periods due to repeated Senecio jacobaea intake. Two other horses had to be excluded after nine and 11 out of 12 observation periods. Only two horses were able to sort out the various amounts (5 and 10% contamination level) of Senecio jacobaea during the whole experiment.

Conclusions

Horses’ intake of Senecio jacobaea cannot be avoided despite being fed with hay ad libitum. Due to the risk of chronic intoxication by pyrrolizidine alkaloids intake, feeding Senecio jacobaea contaminated hay must be avoided, and pastures with Senecio jacobaea growth are considered inappropriate for feed production.
Exome sequencing of glioblastoma-derived cancer stem cells reveals rare clinically relevant frameshift deletion in MLLT1 gene
Authors: Marei Hany E. , Althani Asmaa , Afifi Nahla , Hasan Anwarul , Caceci Thomas , Felsani Armando , Tringali Giuseppe , Cifola Ingrid , Pozzoli Giacomo , Cenciarelli Carlo
Published: January 2022

Background

Glioblastoma multiforme (GBM) is a heterogeneous CNS neoplasm which causes significant morbidity and mortality. One reason for the poor prognostic outcome of GBM is attributed to the presence of cancer stem cells (CSC) which confer resistance against standard chemo- and radiotherapeutics modalities. Two types of GBM-associated CSC were isolated from the same patient: tumor core- (c-CSC) and peritumor tissue-derived cancer stem cells (p-CSC). Our experiments are focused on glioblastoma–IDH-wild type, and no disease-defining alterations were present in histone, BRAF or other genes.

Methods

In the present study, potential differences in genetic variants between c-CSC versus p-CSC derived from four GBM patients were investigated with the aims of (1) comparing the exome sequences between all the c-CSC or p-CSC to identify the common variants; (2) identifying the variants affecting the function of genes known to be involved in cancer origin and development.

Results

By comparative analyses, we identified common gene single nucleotide variants (SNV) in all GBM c-CSC and p-CSC, a potentially deleterious variant was a frameshift deletion at Gln461fs in the MLLT1 gene, that was encountered only in p-CSC samples with different allelic frequency.

Conclusions

We discovered a potentially harmful frameshift deletion at Gln461fs in the MLLT1 gene. Further investigation is required to confirm the presence of the identified mutations in patient tissue samples, as well as the significance of the frameshift mutation in the MLLT1 gene on GBM biology and response to therapy based on genomic functional experiments.
Triglyceride/low-density-lipoprotein cholesterol ratio is the most valuable predictor for increased small, dense LDL in type 2 diabetes patients
Authors: Ouchi Gen , Komiya Ichiro , Taira Shinichiro , Wakugami Tamio , Ohya Yusuke
Published: January 2022

Background

Small, dense low-density lipoprotein (sd-LDL) increases in type 2 diabetes patients and causes arteriosclerosis. Non–high-density-lipoprotein cholesterol (non–HDL-C) is thought to be useful for predicting arteriosclerosis and sd-LDL elevation; however, there are no data about whether the triglyceride /low-density-lipoprotein cholesterol (TG/LDL-C) ratio is a valuable predictor for sd-LDL.

Methods

A total of 110 type 2 diabetes patients with hypertriglyceridemia were analyzed. No patients were treated with fibrates, but 47 patients were treated with statins. LDL-C was measured by the direct method. LDL-migration index (LDL-MI) using electrophoresis (polyacrylamide gel, PAG) was calculated, and a value ≥0.400 was determined to indicate an increase in sd-LDL. Simple regression analyses were carried out between LDL-MI and lipid markers. Receiver operating characteristic curves of lipid markers for predicting high LDL-MI were applied to determine the area under the curve (AUC), sensitivity, specificity, and cut-off point.

Results

LDL-MI correlated negatively with LDL-C (P = 0.0027) and PAG LDL fraction (P < 0.0001) and correlated positively with TGs, non–HDL-C, TG/LDL-C ratio, TG/HDL-C ratio, and non–HDL-C/HDL-C ratio among all study patients. Similar results were obtained for patients analyzed according to statin treatment. The AUCs (95% confidence interval) were 0.945 (0.884-1.000) for TG/LDL-C ratio and 0.614 (0.463-0.765) for non–HDL-C in patients without statins (P = 0.0002). The AUCs were 0.697 (0.507-0.887) for TG/LDL-C and 0.682 (0.500-0.863) for non–HDL-C in patients treated with statins. The optimal cut-off point for TG/LDL-C ratio for increased LDL-MI was 1.1 (molar ratio) regardless of statin treatment. The sensitivity and specificity of the TG/LDL-C ratio (90.0 and 93.9%, respectively) were higher than those of non–HDL-C (56.7 and 78.8%, respectively) in patients without statins.

Conclusions

The TG/LDL-C ratio is a reliable surrogate lipid marker of sd-LDL and superior to non–HDL-C in type 2 diabetes patients not treated with statins.
Roles of plasma leptin and resistin in novel subgroups of type 2 diabetes driven by cluster analysis
Authors: Peng Xuemin , Huang Jiaojiao , Zou Huajie , Peng Bei , Xia Sanshan , Dong Kun , Sun Nan , Tao Jing , Yang Yan
Published: January 2022

Background

A novel classification has been introduced to promote precision medicine in diabetes. The current study aimed to investigate the relationship between leptin and resistin levels with novel refined subgroups in patients with type 2 diabetes mellitus (T2DM).

Methods

The k-means analysis was conducted to cluster 541 T2DM patients into the following four subgroups: mild obesity-related diabetes (MOD), severe insulin-deficient diabetes (SIDD), severe insulin-resistant diabetes (SIRD) and mild age-related diabetes (MARD). Individuals meeting the exclusion criteria were eliminated, the data for 285 patients were analyzed. Characteristics were determined using various clinical parameters. Both the leptin and resistin levels were determined using enzyme-linked immunosorbent assay.

Results

The highest levels of plasma leptin were in the MOD group with relatively lower levels in the SIDD and SIRD groups (P < 0.001). The SIRD group had a higher resistin concentration than the MARD group (P = 0.024) while no statistical significance in resistin levels was found between the SIDD and MOD groups. Logistic regression demonstrated that plasma resistin was associated with a higher risk of diabetic nephropathy (odds ratios (OR) = 2.255, P = 0.001). According to receiver operating characteristic (ROC) curves, the area under the curve (AUC) of resistin (0.748, 95% CI 0.610–0.887) was significantly greater than that of HOMA2-IR (0.447, 95% CI 0.280–0.614) (P < 0.05) for diabetic nephropathy in the SIRD group.

Conclusions

Leptin levels were different in four subgroups of T2DM and were highest in the MOD group. Resistin was elevated in the SIRD group and was closely related to diabetic nephropathy.
Prognostic factors for elderly gastric cancer patients who underwent gastrectomy
Authors: Endo Shunji , Yamatsuji Tomoki , Fujiwara Yoshinori , Higashida Masaharu , Kubota Hisako , Matsumoto Hideo , Tanaka Hironori , Okada Toshimasa , Yoshimatsu Kazuhiko , Sugimoto Ken , Ueno Tomio
Published: January 2022

Background

Patients with gastric cancer are aging in Japan. It is not clear which patients and which surgical procedures have survival benefits after gastrectomy. A multivariate analysis was performed.

Methods

The medical records of 166 patients aged ≥ 80 years who underwent gastrectomy without macroscopic residual tumors were retrospectively reviewed. Univariate and multivariate analyses using Cox proportional hazard models were performed to detect prognostic factors for overall survival.

Results

In univariate analyses, age (≥ 90 vs. ≥ 80, < 85), performance status (3 vs. 0), American Society of Anesthesiologists physical status (ASA-PS) (3, 4 vs. 1, 2), Onodera’s prognostic nutritional index (< 40 vs. ≥ 45), the physiological score of the Physiological and Operative Severity Score for the enUmeration of Mortality and morbidity (POSSUM) (≥ 40 vs. ≥ 20, ≤ 29), surgical approach (laparoscopic vs. open), extent of gastrectomy (total, proximal vs. distal), extent of lymphadenectomy (D1 vs. ≥ D2), pathological stage (II–IV vs. I), and residual tumor (R1 vs. R0) were significantly correlated with worse overall survival. Multivariate analysis revealed that ASA-PS [3, 4 vs. 1, 2, hazard ratio (HR) 2.30, 95% confidence interval (CI) 1.24–4.24], extent of gastrectomy (total vs. distal, HR 2.17, 95% CI 1.10–4.31) (proximal vs. distal, HR 4.05, 95% CI 1.45–11.3), extent of lymphadenectomy (D0 vs. ≥ D2, HR 12.4, 95% CI 1.58–97.7), and pathological stage were independent risk factors for mortality.

Conclusions

ASA-PS was a useful predictor for postoperative mortality. Gastrectomy including cardia is best avoided.
Prognosis and survival analysis of patients with pancreatic cancer: retrospective experience of a single institution
Authors: Li Qi , Feng Zijian , Miao Ruyi , Liu Xun , Liu Chenxi , Liu Zhen
Published: January 2022

Background

The overall survival of patients  with pancreatic cancer is extremely low. Despite multiple large-scale studies, identification of predictors of patient survival remains challenging. This study aimed to investigate the prognostic factors for pancreatic cancer.

Methods

The clinical data of 625 patients with pancreatic cancer treated at Shengjing Hospital of China Medical University from January 2013 to December 2017 were collected.

Results

Of 625 patients, 569 were followed from 1 to 75 months. The median overall survival was 9.3 months. The overall 1-, 3-, and 5-year survival rates were 37.8%, 15.1%, and 10.5%, respectively. Cox proportional hazards model indicated that baseline carbohydrate antigen 199 level, neutrophil-lymphocyte ratio, operative procedure, lymph node metastasis, number of distant organ metastasis, and postoperative adjuvant chemotherapy were independent prognostic factors of patients with pancreatic cancer. Baseline carbohydrate antigen 199 level, degree of weight loss, operative procedure, lymph node metastasis, number of distant organ metastasis, and postoperative adjuvant chemotherapy were independent prognostic factors of pancreatic head cancer subgroup. Baseline carbohydrate antigen 199 level, carcinoembryonic antigen level, total bilirubin level, neutrophil-lymphocyte ratio, peripancreatic invasion, number of distant organ metastasis, and postoperative adjuvant chemotherapy were independent prognostic factors of the pancreatic body/tail cancer subgroup.

Conclusions

Higher carbohydrate antigen 199 levels, neutrophil-lymphocyte ratio, lymph node metastasis and distant organ metastasis predict a poor prognosis in patients with pancreatic cancer. Early detection, early radical surgery and adjuvant chemotherapy are needed to improve prognosis for this deadly disease.
EndMT: New findings on the origin of myofibroblasts in endometrial fibrosis of intrauterine adhesions
Authors: Xu Chengcheng , Bao Meng , Fan Xiaorong , Huang Jin , Zhu Changhong , Xia Wei
Published: January 2022

Background

Intrauterine adhesion (IUA) is one of the leading causes of infertility and the main clinical challenge is the high recurrence rate. The key to solving this dilemma lies in elucidating the mechanisms of endometrial fibrosis. The aim of our team is to study the mechanism underlying intrauterine adhesion fibrosis and the origin of fibroblasts in the repair of endometrial fibrosis.

Methods

Our experimental study involving an animal model of intrauterine adhesion and detection of fibrosis-related molecules. The levels of molecular factors related to the endothelial-to-mesenchymal transition (EndMT) were examined in a rat model of intrauterine adhesion using immunofluorescence, immunohistochemistry, qPCR and Western blot analyses. Main outcome measures are levels of the endothelial marker CD31 and the mesenchymal markers alpha-smooth muscle actin (α-SMA) and vimentin.

Results

Immunofluorescence co-localization of CD31 and a-SMA showed that 14 days after moulding, double positive cells for CD31 and a-SMA could be clearly observed in the endometrium. Decreased CD31 levels and increased α-SMA and vimentin levels indicate that EndMT is involved in intrauterine adhesion fibrosis.

Conclusions

Endothelial cells promote the emergence of fibroblasts via the EndMT during the endometrial fibrosis of intrauterine adhesions.
Advanced magnetic resonance imaging of chronic whiplash patients: a clinical practice-based feasibility study
Authors: Uhrenholt Lars , Brix Lau , Wichmann Thea Overgaard , Pedersen Michael , Ringgaard Steffen , Jensen Tue Secher
Published: January 2022

Background

Whiplash injury is common following road traffic crashes affecting millions worldwide, with up to 50% of the injured developing chronic symptoms and 15% having a reduced working capability due to ongoing disability. Many of these patients receive treatment in primary care settings based upon clinical and diagnostic imaging findings. Despite the identification of different types of injuries in the whiplash patients, clinically significant relationships between injuries and chronic symptoms remains to be fully established. This study investigated the feasibility of magnetic resonance imaging (MRI) techniques including quantitative diffusion weighted imaging and measurements of cerebrospinal fluid (CSF) flow as novel non-invasive biomarkers in a population of healthy volunteers and chronic whiplash patients recruited from a chiropractic clinic for the purpose of improving our understanding of whiplash injury.

Methods

Twenty chronic whiplash patients and 18 healthy age- and gender matched control subjects were included [mean age ± SD (sex ratio; females/males), case group: 37.8 years ± 9.1 (1.22), control group: 35.1 years ± 9.2 (1.25)]. Data was collected from May 2019 to July 2020. Data from questionnaires pertaining to the car crash, acute and current symptoms were retrieved and findings from clinical examination and MRI including morphologic, diffusion weighted and phase-contrast images were recorded. The apparent diffusion coefficient and fractional anisotropy were calculated, and measurement and analysis of CSF flow was conducted. Statistical analyses included Fisher’s exact test, Mann Whitney U test and analysis of variance between groups.

Results

The studied population was described in detail using readily available clinical tools. No statistically significant differences were found between the groups on MRI.

Conclusions

This study did not show that MRI‐based measures of morphology, spinal cord and nerve root diffusion or cerebrospinal fluid flow are sensitive biomarkers to distinguish between chronic whiplash patients and healthy controls. The detailed description of the chronic whiplash patients using readily available clinical tools may be of great relevance to the clinician. In the context of feasibility, clinical practice-based advanced imaging studies with a technical setup similar to the presented can be expected to have a high likelihood of successful completion.
Operating room efficiency in a low resource setting: a pilot study from a large tertiary referral center in Ethiopia
Authors: Negash Samuel , Anberber Endale , Ayele Blen , Ashebir Zeweter , Abate Ananya , Bitew Senait , Derbew Miliard , Weiser Thomas G. , Starr Nichole , Mammo Tihitena Negussie
Published: January 2022

Background

The operating room (OR) is one of the most expensive areas of a hospital, requiring large capital and recurring investments, and necessitating efficient throughput to reduce costs per patient encounter. On top of increasing costs, inefficient utilization of operating rooms results in prolonged waiting lists, high rate of cancellation, frustration of OR personnel as well as increased anxiety that negatively impacts the health of patients. This problem is magnified in developing countries, where there is a high unmet surgical need. However, no system currently exists to assess operating room utilization in Ethiopia.

Methodology

A prospective study was conducted over a period of 3 months (May 1 to July 31, 2019) in a tertiary hospital. Surgical case start time, end time, room turnover time, cancellations and reason for cancellation were observed to evaluate the efficiency of eight operating rooms.

Results

A total of 933 elective procedures were observed during the study period. Of these, 246 were cancelled, yielding a cancellation rate of 35.8%. The most common reasons for cancellation were related to lack of OR time and patient preparation (8.7% and 7.7% respectively). Shortage of facilities (instrument, blood, ICU bed) were causes of cancelation in 7.7%. Start time was delayed in 93.4% (mean 8:56 am ± 52 min) of cases. Last case completion time was early in 47.9% and delayed in 20.6% (mean 2:54 pm ± 156 min). Turnover time was prolonged in 34.5% (mean 25 min ± 49 min). Total operating room utilization ranged from 10.5% to 174%. Operating rooms were underutilized in 42.7% while overutilization was found in 14.6%.

Conclusion

We found a high cancellation rate, most attributable to late start times leading to delays for the remainder of cases, and lack of preoperative patient preparation. In a setting with a high unmet burden of surgical disease, OR efficiency must be maximized with improved patient evaluation workflows, adequate OR staffing and commitment to punctual start times. We recommend future quality improvement projects focusing on these areas to increase OR efficiency.
Optimal transport- and kernel-based early detection of mild cognitive impairment patients based on magnetic resonance and positron emission tomography images
Authors: Liu Ziyu , Johnson Travis S. , Shao Wei , Zhang Min , Zhang Jie , Huang Kun
Published: January 2022

Background

To help clinicians provide timely treatment and delay disease progression, it is crucial to identify dementia patients during the mild cognitive impairment (MCI) stage and stratify these MCI patients into early and late MCI stages before they progress to Alzheimer’s disease (AD). In the process of diagnosing MCI and AD in living patients, brain scans are collected using neuroimaging technologies such as computed tomography (CT), magnetic resonance imaging (MRI), or positron emission tomography (PET). These brain scans measure the volume and molecular activity within the brain resulting in a very promising avenue to diagnose patients early in a minimally invasive manner.

Methods

We have developed an optimal transport based transfer learning model to discriminate between early and late MCI. Combing this transfer learning model with bootstrap aggregation strategy, we overcome the overfitting problem and improve model stability and prediction accuracy.

Results

With the transfer learning methods that we have developed, we outperform the current state of the art MCI stage classification frameworks and show that it is crucial to leverage Alzheimer’s disease and normal control subjects to accurately predict early and late stage cognitive impairment.

Conclusions

Our method is the current state of the art based on benchmark comparisons. This method is a necessary technological stepping stone to widespread clinical usage of MRI-based early detection of AD.
Fatal liver mass rupture in a common-variable-immunodeficiency patient with probable nodular regenerating hyperplasia
Authors: Sompornrattanaphan Mongkhon , Tongdee Ranista , Wongsa Chamard , Jitmuang Anupop , Thongngarm Torpong
Published: January 2022

Background

Nodular regenerating hyperplasia (NRH) is the most common liver involvement in common variable immunodeficiency (CVID). Most patients are asymptomatic with gradually increasing alkaline phosphatase (ALP) and mildly elevated transaminase enzymes over the years. We report the first case of fatal liver mass rupture in a CVID patient with probable NRH.

Case presentation

A 24-year-old man was diagnosed with CVID at the age of 1.25 years. Genetic testing revealed a transmembrane activator and calcium-modulator and cyclophilin-ligand interactor (TACI) mutation. He had been receiving intravenous immunoglobulin (IVIg) replacement therapy ever since then. The trough level of serum IgG ranged between 750–1200 mg/dL. However, he still had occasional episodes of lower respiratory tract infection until bronchiectasis developed. At 22 years old, computed tomography (CT) chest and abdomen as an investigation for lung infection revealed incidental findings of numerous nodular arterial-enhancing lesions in the liver and mild splenomegaly suggestive of NRH with portal hypertension. Seven months later, he developed sudden hypotension and tense bloody ascites. Emergency CT angiography of the abdomen showed NRH with intrahepatic hemorrhage and hemoperitoneum. Despite successful gel foam embolization, the patient died from prolonged shock and multiple organ failure.

Conclusions

Although CVID patients with NRH are generally asymptomatic, late complications including portal hypertension, hepatic failure, and hepatic rupture could occur. Therefore, an evaluation of liver function should be included in the regular follow-up of CVID patients.
Triple dislocation around the knee joint: a case report
Authors: Chew Ernest , Sharma Aadhar , Gupte Chinmay
Published: January 2022

Background

Dislocation of the knee is a serious and potentially limb-threatening injury. There are three types of dislocation around the knee joint: patellofemoral, tibiofemoral, and tibiofibular. Tibiofemoral dislocation is the variant that is deemed the most serious, with a higher risk of compromise to the popliteal artery and common peroneal nerve. Although simultaneous dislocations of two types have been described, there has been no such description of all three types occurring simultaneously.

Case presentation

We present a case of a 40-year-old hairdresser who suffered a fall off her moped in Spain, and simultaneously dislocated all three articulations around the knee. Diagnosis was achieved with clinical examination, plain films, and computed tomography and magnetic resonance imaging scans. Management consisted of initial surgical debridement and reduction with stabilization of the affected joints.

Conclusion

Dislocation of the knee is an uncommon but life changing and potentially limb-threatening injury. It should always be suspected in trauma patients who present with multiligamentous knee injuries. The main concern is of neurovascular compromise to the lower leg, namely, the popliteal artery and common peroneal nerve. The treatment of multiligamentous knee injuries for most patients is surgical treatment with physiotherapy and adequate stabilization of the knee joint. Close monitoring of progress of the knee in terms of persistent laxity, range of movement, and functional status is required for at least 1-year post injury. Current evidence suggests that, despite good functional outcomes for knee dislocations in the short term, the prevalence of post-traumatic osteoarthritis is high in the long term.
PACK-CXL vs. antimicrobial therapy for bacterial, fungal, and mixed infectious keratitis: a prospective randomized phase 3 trial
Authors: Hafezi Farhad , Hosny Mohammed , Shetty Rohit , Knyazer Boris , Chen Shihao , Wang Qinmei , Hashemi Hassan , Torres-Netto Emilio A. ,   the PACK-CXL Working Group, Zhang Hanxiao , Bora’i Ashraf , Tawfeek Mohamed , Nagaraja Harsha , D’Souza Sharon , Asgari Soheila , Mirsalim Agha , Chorny Alexander , Krakauer Yonit , Pajic Bojan , Gilardoni Francesca , Hafezi Nikki , Hillen Mark , Liu Nanji , Boldi Marc-Olivier , Tabibian David , Torgerson Paul R. , Zbinden Reinhard , Koliwer-Brandl Hendrik , Bradley Randleman J.
Published: January 2022

Background

Infectious keratitis is a major cause of global blindness. We tested whether standalone photoactivated chromophore corneal cross-linking (PACK-CXL) may be an effective first-line treatment in early to moderate infectious keratitis, compared with standard antimicrobial treatment.

Methods

This is a randomized, controlled, multinational phase 3 clinical trial. Participants in five centers in Egypt, India, Iran, Israel, and China, aged ≥ 18 years, with infectious keratitis of presumed bacterial, fungal, or mixed origin, were randomly assigned (1:1) to PACK-CXL, or antimicrobial therapy. Outcomes measures included healing, defined as time to re-epithelialization of the corneal epithelial defect in the absence of inflammatory activity in the anterior chamber and clearance of stromal infiltrates. Treatment success was defined as the complete resolution of signs of infection.

Results

Between July 21, 2016, and March 4, 2020, participants were randomly assigned to receive PACK-CXL (n = 18) or antimicrobial therapy per American Academy of Ophthalmology (AAO) guidelines (n = 21). No participants were lost to follow-up. Four eyes were excluded from the epithelialization time analysis due to treatment failure: two in the antimicrobial therapy group, and two in the PACK-CXL group. Success rates were 88.9% (16/18 patients) in the PACK-CXL group and 90.5% (19/21 patients) in the medication group. There was no significant difference in time to complete corneal re-epithelialization (P = 0.828) between both treatment groups.

Conclusions

PACK-CXL may be an alternative to antimicrobial drugs for first-line and standalone treatment of early to moderate infectious keratitis of bacterial or fungal origin.

Trial registration This trial is registered at ClinicalTrials.gov, trial registration number: NCT02717871
Application of artificial intelligence in cataract management: current and future directions
Authors: Gutierrez Laura , Lim Jane Sujuan , Foo Li Lian , Ng Wei Yan , Yip Michelle , Lim Gilbert Yong San , Wong Melissa Hsing Yi , Fong Allan , Rosman Mohamad , Mehta Jodhbir Singth , Lin Haotian , Ting Darren Shu Jeng , Ting Daniel Shu Wei
Published: January 2022

The rise of artificial intelligence (AI) has brought breakthroughs in many areas of medicine. In ophthalmology, AI has delivered robust results in the screening and detection of diabetic retinopathy, age-related macular degeneration, glaucoma, and retinopathy of prematurity. Cataract management is another field that can benefit from greater AI application. Cataract  is the leading cause of reversible visual impairment with a rising global clinical burden. Improved diagnosis, monitoring, and surgical management are necessary to address this challenge. In addition, patients in large developing countries often suffer from limited access to tertiary care, a problem further exacerbated by the ongoing COVID-19 pandemic. AI on the other hand, can help transform cataract management by improving automation, efficacy and overcoming geographical barriers. First, AI can be applied as a telediagnostic platform to screen and diagnose patients with cataract using slit-lamp and fundus photographs. This utilizes a deep-learning, convolutional neural network (CNN) to detect and classify referable cataracts appropriately. Second, some of the latest intraocular lens formulas have used AI to enhance prediction accuracy, achieving superior postoperative refractive results compared to traditional formulas. Third, AI can be used to augment cataract surgical skill training by identifying different phases of cataract surgery on video and to optimize operating theater workflows by accurately predicting the duration of surgical procedures. Fourth, some AI CNN models are able to effectively predict the progression of posterior capsule opacification and eventual need for YAG laser capsulotomy. These advances in AI could transform cataract management and enable delivery of efficient ophthalmic services. The key challenges include ethical management of data, ensuring data security and privacy, demonstrating clinically acceptable performance, improving the generalizability of AI models across heterogeneous populations, and improving the trust of end-users.
Slight femoral under-correction versus neutral alignment in total knee arthroplasty with preoperative varus knees: a comparative study
Authors: Lei Kai , Liu Li-Ming , Yang Peng-Fei , Xiong Ran , Fu De-Jie , Yang Liu , Guo Lin
Published: January 2022

Background

This study aimed to compare the short-term clinical results of slight femoral under-correction with neutral alignment in patients with preoperative varus knees who underwent total knee arthroplasty.

Methods

The medical records and imaging data were retrospectively collected from patients who had undergone total knee arthroplasty in our hospital from January 2016 to June 2019. All patients had varus knees preoperatively. Upon 1:1 propensity score matching, 256 patients (256 knees) were chosen and divided into a neutral alignment group (n=128) and an under-correction group (n=128). The patients in the neutral group were treated with the neutral alignment. In the under-correction group, the femoral mechanical axis had a 2° under-correction. The operative time, tourniquet time and the length of hospital stay in the two groups were recorded. The postoperative hip-knee-ankle angle, frontal femoral component angle and frontal tibial component angle were measured. Patient-reported outcome measures were also compared.

Results

The operative time, tourniquet time and the length of hospital stay in the under-correction group were significantly shorter than the neutral alignment group (P<0.05). At the 2-year follow-up, the under-correction group had a larger varus alignment (P<0.05) and a larger frontal femoral component angle (P<0.05), and the frontal tibial component angles of the two groups were comparable. Compared with the neutral alignment group, the slight femoral under-correction group had significantly better patient-reported outcome measures scores (P<0.05).

Conclusion

For varus knees treated with total knee arthroplasty, alignment with a slight femoral under-correction has advantages over the neutral alignment in terms of the shorter operative time and better short-term clinical results.

Level of evidence

III
Depression symptoms and associated factors among thalassemia patients in the Palestinian Territories: a cross-sectional study
Authors: Sarhan Adnan Lutfi , Modallal Shahenaz , Mahamid Fayez Azez , Berte Denise Ziya
Published: January 2022

Background

Thalassemia is a condition that causes the human body to destroy red blood cells faster than they can be made. It causes physical symptomology as well as psychological distress. The current study aimed to identify the prevalence of depression symptoms among individuals with moderate to severe thalassemia. A quantitative descriptive cross-sectional design was applied utilizing the Beck Depression Inventory to assess the level of depression in the sample.

Results

Some significant relationships were demonstrated in the sample: males reporting severe depression symptoms than females by 6.0 times (95% CI 0.07–0.62,p0.014), and reporting moderate depression symptoms (95% CI 0.00–0.47,p0.05). Additionally, income was found to be a predictor of level of depression symptoms with low income reported higher incidence of severe depression symptoms than those whose monthly income was > 400$ by 18.4 times (95% CI 0.38–1.03,p≤ 0.001), but not reporting a significant association between moderate depressive symptoms and monthly income (95% CI − 012–1.47,P0.225). A significant association was found between the educational attainment and level of depression symptoms with lower levels of education predicting higher levels of severe depression symptoms (95% CI 0.069–0.89,p0.022), but no significant association was reported between moderate depression symptoms and educational attainment (95% CI − 0.49–0.01,p0.81).

Related to disease characteristics a relationship was confirmed between severe depressive symptoms and medication level such as the individual needing tablets or pumps (95% CI 0.189–1.05,p0.005 and 95% CI 0.52–1.44,p0.001) respectively. Other disease related variables showed no significant correlation with depressive symptom levels.

Additional significant relationships were found in environment whereas increased moderate depressive symptoms were experienced by individuals residing in rural areas as opposed to those living in IDP camps or cities by 4 times (95% CI − 0.30–0.01,p0.04), but no significant association was found between severe depression and the place of residence. The other independent variables had no significant correlation with severe or moderate depressive symptoms.

Conclusion

In light of these findings addressing symptoms of depression directly and supporting patients with thalassemia with basic life needs unrelated to their disease maybe mitigating depressive symptoms which may negatively affect recovery.
Late acute cellular rejection after switch to everolimus monotherapy at 11 months following liver transplantation
Authors: Razafindrazoto Chantelli Iamblaudiot , Trystram Noémie , Martins Gustavo Miranda , Stern Christiane , Charlotte Frédéric , Lebray Pascal
Published: January 2022

Background

Acute cellular rejection beyond the 6th month posttransplant is an uncommon complication after liver transplantation. The inadequate immunosuppression (IS) remains the main risk factor. We report a case of acute cellular rejection after a switch to everolimus monotherapy at 11 months following liver transplantation.

Case presentation

This was a 69-year-old man who underwent liver transplantation after hepatocellular carcinoma. The initial immunosuppression was a combination of three immunosuppressive drugs (corticosteroids + tacrolimus + mycophenolate mofetil). The corticosteroid therapy was stopped at the 4th month posttransplant. Serious side effects of the immunosuppressive drugs (agranulocytosis and renal dysfunction), which occurred 4 months after transplantation, required a reduction and then a discontinuation of tacrolimus and mycophenolate mofetil. Everolimus was introduced as a replacement. The patient was consulted at 11 months after liver transplantation, 1 month after stopping the two immunosuppressive drugs, for liver function test abnormalities such as cytolysis and anicteric cholestasis. A moderate late acute cellular rejection was confirmed by a liver biopsy. A satisfactory biological evolution was observed following corticosteroid boluses and optimization of basic immunosuppressive drugs.

Conclusion

Late acute cellular rejection remains an uncommon complication, observed mostly in the first year after liver transplantation. The main risk factor is usually the decrease of immunosuppression.
Thalidomide-based inhibitor for TNF-α: designing and Insilico evaluation
Authors: Shivaleela Biradar , Srushti S. C. , Shreedevi S. J. , Babu R. L.
Published: January 2022

Background

Inflammatory diseases are the vast array of disorders caused by inflammation. During most inflammatory events, many cytokines expressions were modulated, and one such cytokine is tumor necrosis factor-alpha (TNF-α). TNF-α is mainly secreted by monocytes and macrophages. Notably, it has been proposed as a therapeutic target for several diseases. The anti-TNF biology approach is mainly based on monoclonal antibodies. The fusion protein and biosimilars are prevalent in treating inflammation for decades. Only a few small molecule inhibitors are available to inhibit the expression of TNF-α, and one such promising drug was thalidomide. Therefore, the study was carried out to design thalidomide-based small molecule inhibitors for TNF-α. The main objective of our study is to design thalidomide analogs to inhibit TNF-α using the insilico approach.

Results

Several thalidomide analogs were designed using chemsketch. After filtration of compounds through ‘Lipinski rule of 5’ by Molinspiration tool, as a result, five compounds were selected. All these compounds were subjected to molecular docking, and the study showed that all five compounds had good binding energy. However, based on ADMET predictions, two compounds (S3 and S5) were eliminated.

Conclusions

Our preliminary results suggest that S1, S2, S4 compounds showed potential ligand binding capacity with TNF-α and, interestingly, with limited or no toxicity. Our preliminary investigation and obtained results have fashioned more interest for further in vitro studies.
Delivering mental healthcare to patients with a depressive disorder alongside a life-limiting illness
Authors: Hughes Daniel , Yardley Sarah , Greenfield Philippa , Rolph Martin
Published: January 2022

The concurrent assessment and treatment of mental health disorders and palliative illnesses is complex. Affective disorders are more prevalent in people who need palliative care. Identifying the most suitable place of care and multi-professional multidisciplinary teams to provide support can be challenging and bewildering for professionals and patients. Mental health clinicians may be left with a sense of therapeutic nihilism, while palliative care teams can feel limited by the mental health resources available for treating those living with significant physical and mental health needs. We discuss the fictional case of a gentleman with metastatic bowel cancer who has developed symptoms of depressive disorder and identify how taking a pragmatic patient-centred approach can offer a route through potential dilemmas when seeking to provide individualised care based on needs. We used lay person experience alongside our own experiences of novel mechanisms for cross-specialty working in order to direct psychiatric trainees’ approaches to such cases.
The effectiveness of gaming interventions for depression and anxiety in young people: systematic review and meta-analysis
Authors: Townsend Christopher , Humpston Clara , Rogers Jack , Goodyear Victoria , Lavis Anna , Michail Maria
Published: January 2022

Background

Recent research has investigated the use of serious games as a form of therapeutic intervention for depression and anxiety in young people.

Aims

To conduct a systematic review and meta-analysis into the effectiveness of gaming interventions for treating either depression or anxiety in individuals aged 12–25 years.

Method

An electronic search was conducted on the 30 March 2020, using PsycINFO, ISI Web of Science Core Collection, Medline and EMBASE databases. Standardised effect sizes (Hedge's g) were calculated for between-participant comparisons between experimental (therapeutic intervention) and control conditions, and within-participant comparisons between pre- and post-intervention time points for repeated measures designs.

Results

Twelve studies (seven randomised controlled trials (RCTs) and five non-randomised studies) were included. For RCTs, there was a statistically significant and robust effect (g = −0.54, 95% CI −1.00 to −0.08) favouring the therapeutic intervention when treating youth depression. For non-RCTs, using a repeated measures design, the overall effect was also strong (g = −0.75, 95% CI −1.64 to 0.14) favouring therapeutic intervention, but this was not statistically significant. Interestingly, we found no statistically significant effect for treating youth anxiety.

Conclusions

There is preliminary evidence to suggest that gaming interventions are an effective treatment for youth depression, but not anxiety. Further research is warranted to establish the utility, acceptability and effectiveness of gaming interventions in treating mental health problems in young people.