Miracle-dz/UniFAR-FTUs huggingface dataset:
Interpretability for Conditional Average Treatment Effect Estimation

Machine learning has recently shown much potential for causal inference tasks in several important fields. Of particular interest is the estimation of individual-level treatment effects in the context of precision medicine, which can provide clinicians with crucial information for the design and issuance of patient-specific treatment plans. This implies answering questions of the type: “Will chemotherapy increase the life expectancy of this oncologic patient? ” However, to effectively integrate machine learning models in the medical setting, they must also be interpretable, so that clinicians can understand and validate their decisions. Surprisingly, little attention has been paid to the intersection of the two fields – individual treatment effect estimation and interpretability – and the only works that explicitly consider it frame the problem as interpreting a standard supervised learning setting, ignoring the idiosyncrasies of the treatment effect estimation problem. The present work proposes a framework for interpreting the Conditional Average Treatment Effect (CATE) estimation problem. By examining the unique features of the CATE setting, our method allows identification of the information that is of the utmost importance in the design of personalized policies: the predictive covariates. Furthermore, the solid theoretical formalization of the framework enables an extensive characterization of patients at the individual level, for instance, by additionally disentangling the prognostic and irrelevant covariates and uncovering the specific features that make a treatment more or less efficacious for an individual compared to the average population. The proposed framework is extensively evaluated in both synthetic and real-world experiments. We present use-cases to provide practitioners with specific guidelines on using the framework, for example, by identifying which covariates determine the increase in cognitive test scores for premature children that join a health development program. Finally, we characterize four popular CATE estimators based on their ability to disentangle the predictive covariates. We do so in several synthetic datasets inspired by the drug development setting, thus providing insights on design choices by outlining the estimators’ virtues and limitations in various scenarios. We therefore show how our method can serve as a tool for model selection, which is naturally challenging in causal inference tasks.
Imaging visuospatial memory in temporal lobe epilepsy—Results of an fMRI study

Purpose Impairment of cognitive functions is commonly observed in temporal lobe epilepsy (TLE). The aim of this study was to assess visuospatial memory functions and memory-related networks using an adapted version of Roland’s Hometown Walking (RHWT) functional MRI (fMRI) task in patients with TLE. Methods We used fMRI to study activation patterns based on a visuospatial memory paradigm in 32 TLE patients (9 right; 23 left) and also within subgroups of lesional and non-lesional TLE. To test for performance, a correlational analysis of fMRI activation patterns and out-of-scanner neuropsychological visuospatial memory testing was performed. Additionally, we assessed memory-related networks using functional connectivity (FC). Results Greater contralateral than ipsilateral mesiotemporal (parahippocampal gyrus/hippocampus) activation was observed in left (n = 23)/right (n = 9) TLE. In lesional left TLE (n = 17), significant activations were seen in right more than left mesiotemporal areas (parahippocampal gyrus), while non-lesional left TLE patients (n = 6) showed significant bilateral (left>right) activations in mesiotemporal structures (parahippocampal gyrus). In left TLE, visuospatial cognitive testing correlated with fMRI activations in left (parahippocampal gyrus) and right mesiotemporal structures (hippocampus), characterized by greater fMRI activation being associated with better memory scores. In right TLE, higher scores in visuospatial memory testing were associated with greater fMRI activations in left and right insular regions. FC patterns of memory-related networks differ in right and left TLE. Conclusion While TLE in general leads to asymmetrical mesiotemporal activation, lesion-induced and non-lesional TLE patients reveal different memory fMRI activation patterns. In right TLE, insular regions try to compensate for impaired right mesiotemporal structures during the performance of visuospatial tasks. Underlying functional visuospatial memory networks differ in right and left TLE.
Health-Related Quality of Life Among Patients With Sickle Cell Disease in an Adult Hematology Clinic in a Tertiary Hospital in Lagos, Nigeria

Background Sickle cell disease (SCD) is a genetic disease of public health concern. Improved quality healthcare has increased the life expectancy of these patients; however, they also face an increased frequency of vaso-occlusive crises and other SCD complications. These complications affect their quality of life, an area of care, which healthcare providers often overlook. We sought to determine the health-related quality of life among patients living with sickle cell disease in Lagos, Nigeria. Materials and methods We conducted a cross-sectional study of 198 patients with sickle cell disease who attended the adult sickle cell clinic at a tertiary hospital in Lagos, Nigeria, during the period from October 1, 2018, to February 28, 2019. A self-administered questionnaire was used to obtain the clinical and socio-demographic characteristics of the patients and the 35-item Short-Form Health Survey (SF-36) questionnaire was used to determine their health-related quality of life (HRQoL). Determinants of HRQoL were established using bivariate and multivariate regression analysis. Results The mean age of the 198 patients who participated in the study was 28.4±9.1 years, mean steady-state hemoglobin was 8.2 ± 1.3 g/dl, and 85 (42.9%) patients had a monthly income of 150 USD or less. In the previous year, 65 (32.1 %) and 33 (16.6%) patients, respectively, suffered one to two episodes (s) of acute bone pain crises and acute chest syndrome, and 43 (24.7%) had blood transfusion. Using the scoring system for SF-36 provided by RAND Health, role limitation due to physical health had the lowest median score of 50 (interquartile range {IQR}: 0-100). On bivariate analysis, bone pain crisis was associated with statistically significant low scores across all the 8 HRQoL domains of the SF36 questionnaire. Other variables, including having received blood transfusion, recent hospitalization, acute chest syndrome, lower level of income, and younger age, were also associated with significantly low scores. On regression analysis, bone pain crisis, level of income, and acute chest syndrome were found to be independent determinants of quality of life in the patients. Conclusion Sickle cell disease has a negative impact on the health-related quality of life of those affected. The presence of bone pain crisis is an important predictor of health-related quality of life in sickle cell disease patients. To improve patient outcomes, healthcare providers should take a holistic approach in evaluating and managing this disease, taking into cognizance how the complications and the financial burden of this disease impact the quality of life of affected patients.
Multimodal Evoked Potentials as Potential Biomarkers of Disease Activity in Patients With Clinically Isolated Syndrome

Objective There is an ongoing search for markers useful in monitoring and predicting disease activity at the early stage of multiple sclerosis (MS). The goals of this study were to prospectively evaluate the changes in parameters of multimodal evoked potentials (EP) and cognition within a 3-year follow-up period in patients with clinically isolated syndrome (CIS), and to assess the prognostic value of baseline findings with regard to the disease outcomes. Methods In 29 patients (20 women, nine men, mean age 31.1) multimodal (visual, brainstem auditory, somatosensory, event-related) EP and neuropsychological tests (NT) were performed at baseline (T0) and after 1 (T1) and 3 (T3) years. Their results were compared longitudinally between baseline, T1, and T3. Baseline results confirmed conversion of CIS into multiple sclerosis (MS) and disability level at T1 and T3 using multiple comparisons and a logistic regression model. Results Apart from mean N13/P16 SEP (somatosensory evoked potentials) amplitude (lower at T1 and T3 than at baseline (T0 1.02 ± 0.37 μV, T1 0.90 ± 0.26 μV, T3 0.74 ± 0.32 μV, p < 0.05 for both comparisons), no significant changes of EP or NT parameters were found in longitudinal assessment. Baseline P300 Pz latency was longer for the patients with MS than for those with CIS at T1 (352.69 vs. 325.56 ms). No predictive value was shown for any of the analyzed baseline variables with regard to conversion from CIS into MS. Significance Baseline ERP abnormalities were associated with their short-term conversion into MS. ERP are worth considering in multimodal EP evaluation at the early stage of MS.
A lethal model of Leptospira infection in hamster nasal mucosa

Leptospirosis is a fatal zoonosis caused by contact between skin or a mucosal surface and contaminated soil or water. Hamsters were infected by intraperitoneal injection fto establish experimental leptospirosis, which is not a natural route of infection. There are no reports of nasal mucosal infection in hamsters. In this study, infection of the nasal mucosa was performed to establish a model of natural infection. Both methods of infection can cause lethal models with similar symptoms in the later stages of infection, such as weight loss, blood concentration, increased neutrophils (GRAN), and decreased lymphocytes (LYM) in the blood, severe organ damage and liver function obstruction. The burden of Leptospira in the organs and blood was lower in the mucosal inoculation groups at 1 day after infection. However, mucosal infection induced a higher Leptospira burden in urine than intraperitoneal infection in the late stages of infection. After nasal mucosal infection, antibody levels were higher and lasted longer. These results indicated that the route of nasal mucosal infection is a good choice for studying leptospirosis in hamsters.
Mortality risk prediction of high-sensitivity C-reactive protein in suspected acute coronary syndrome: A cohort study

Background There is limited evidence on the use of high-sensitivity C-reactive protein (hsCRP) as a biomarker for selecting patients for advanced cardiovascular (CV) therapies in the modern era. The prognostic value of mildly elevated hsCRP beyond troponin in a large real-world cohort of unselected patients presenting with suspected acute coronary syndrome (ACS) is unknown. We evaluated whether a mildly elevated hsCRP (up to 15 mg/L) was associated with mortality risk, beyond troponin level, in patients with suspected ACS. Methods and findings We conducted a retrospective cohort study based on the National Institute for Health Research Health Informatics Collaborative data of 257,948 patients with suspected ACS who had a troponin measured at 5 cardiac centres in the United Kingdom between 2010 and 2017. Patients were divided into 4 hsCRP groups (<2, 2 to 4.9, 5 to 9.9, and 10 to 15 mg/L). The main outcome measure was mortality within 3 years of index presentation. The association between hsCRP levels and all-cause mortality was assessed using multivariable Cox regression analysis adjusted for age, sex, haemoglobin, white cell count (WCC), platelet count, creatinine, and troponin. Following the exclusion criteria, there were 102,337 patients included in the analysis (hsCRP <2 mg/L (n = 38,390), 2 to 4.9 mg/L (n = 27,397), 5 to 9.9 mg/L (n = 26,957), and 10 to 15 mg/L (n = 9,593)). On multivariable Cox regression analysis, there was a positive and graded relationship between hsCRP level and mortality at baseline, which remained at 3 years (hazard ratio (HR) (95% CI) of 1.32 (1.18 to 1.48) for those with hsCRP 2.0 to 4.9 mg/L and 1.40 (1.26 to 1.57) and 2.00 (1.75 to 2.28) for those with hsCRP 5 to 9.9 mg/L and 10 to 15 mg/L, respectively. This relationship was independent of troponin in all suspected ACS patients and was further verified in those who were confirmed to have an ACS diagnosis by clinical coding. The main limitation of our study is that we did not have data on underlying cause of death; however, the exclusion of those with abnormal WCC or hsCRP levels >15 mg/L makes it unlikely that sepsis was a major contributor. Conclusions These multicentre, real-world data from a large cohort of patients with suspected ACS suggest that mildly elevated hsCRP (up to 15 mg/L) may be a clinically meaningful prognostic marker beyond troponin and point to its potential utility in selecting patients for novel treatments targeting inflammation. Trial registration ClinicalTrials.gov - NCT03507309
The Correlation Between Surgical Procedures and Quality of Life Among Sickle Cell Disease Patients: A Perspective Saudi Study

Introduction: Sickle cell disease (SCD) is among the common prevalent diseases in Saudi Arabia. It is associated with several complications that sometimes necessitate surgical procedures. Those patients can also have a lower quality of life (QoL) due to several reasons. Our aim in this study is to highlight the association between sociodemographic data, clinical data, and SCD-related surgeries in patients with their QoL. Methods: A cross-sectional study was performed using a validated Arabic version of the World Health Organization QoL-BREF (WHOQOL-BREF) questionnaire distributed in electronic form. Male and female Arabic speakers (18+ years old) of Saudi origin were included in this study; those who did not meet these criteria were excluded. Results: We distributed 309 questionnaires to the targeted subjects; however, only 204 met our inclusion criteria. Our findings revealed 135 female respondents and 69 male respondents. Interestingly, splenectomy was not significantly associated with a difference in all aspects of QoL in SCD patients. However, the data showed significantly lower respective mean scores for physical health (p=0.002 & p=0.022) and overall QoL (p=0.024 & p=0.042) for those who underwent cholecystectomy and hip arthroplasty. In contrast, shoulder arthroplasty appeared to be associated with significantly lower mean scores for physical health (T=-2.597; p=0.010) and the environmental aspect of QoL (T=-2.016; p=0.045). Conclusion: Cholecystectomy, hip arthroplasty, and shoulder arthroplasty were significantly associated with lower QoL in SCD patients.
Body fat prediction through feature extraction based on anthropometric and laboratory measurements

Obesity, associated with having excess body fat, is a critical public health problem that can cause serious diseases. Although a range of techniques for body fat estimation have been developed to assess obesity, these typically involve high-cost tests requiring special equipment. Thus, the accurate prediction of body fat percentage based on easily accessed body measurements is important for assessing obesity and its related diseases. By considering the characteristics of different features (e.g. body measurements), this study investigates the effectiveness of feature extraction for body fat prediction. It evaluates the performance of three feature extraction approaches by comparing four well-known prediction models. Experimental results based on two real-world body fat datasets show that the prediction models perform better on incorporating feature extraction for body fat prediction, in terms of the mean absolute error, standard deviation, root mean square error and robustness. These results confirm that feature extraction is an effective pre-processing step for predicting body fat. In addition, statistical analysis confirms that feature extraction significantly improves the performance of prediction methods. Moreover, the increase in the number of extracted features results in further, albeit slight, improvements to the prediction models. The findings of this study provide a baseline for future research in related areas.
A systematic review of the impacts of oral tetracycline class antibiotics on antimicrobial resistance in normal human flora

Abstract Objectives There is interest in doxycycline as prophylaxis against sexually transmitted infections (STIs), but concern about antimicrobial resistance (AMR). We conducted a systematic review (CRD42021273301) of the impact of oral tetracycline-class antibiotics on AMR in normal flora. Methods We searched MEDLINE, EMBASE, the Cochrane Library (1940–2021) and conference proceedings (2014–21) for randomized controlled trials in adults comparing daily oral tetracycline-class antibiotics to non-tetracycline controls. The primary outcome was AMR to tetracyclines; secondary outcomes included resistance to non-tetracyclines. Data were inappropriate for meta-analysis, so we analysed findings descriptively. Results Our search yielded 6265 abstracts of which 7 articles fulfilled inclusion criteria. Most were at moderate/high risk of bias, generally due to inadequate methodologic reporting. Studies used doxycycline, tetracycline, oxytetracycline or minocycline for 2–18 weeks. Most observed an increased burden of tetracycline resistance, including in subgingival (n = 3 studies), gastrointestinal (n = 2) and upper respiratory tract (n = 1) flora; one study of skin flora found no change in tetracycline-resistant Propionibacterium species after 18 weeks of oxytetracycline/minocycline. Four studies reassessed AMR at 2–50 weeks post-intervention and reported varying degrees of resistance. Three articles reported on the prevalence of non-tetracycline AMR after doxycycline prophylaxis, of which one found a transient increase among gastrointestinal Escherichia coli; the other two showed no difference from control. Conclusions Although the effects are modest and transient, limited data from small prospective studies may suggest that oral tetracyclines for 2–18 weeks increase resistance in subgingival, gastrointestinal and upper respiratory tract flora. STI prophylaxis trials should include AMR in commensal bacteria as study outcomes.
LRRK2 dynamics analysis identifies allosteric control of the crosstalk between its catalytic domains

The 2 major molecular switches in biology, kinases and GTPases, are both contained in the Parkinson disease–related leucine-rich repeat kinase 2 (LRRK2). Using hydrogen–deuterium exchange mass spectrometry (HDX-MS) and molecular dynamics (MD) simulations, we generated a comprehensive dynamic allosteric portrait of the C-terminal domains of LRRK2 (LRRK2RCKW). We identified 2 helices that shield the kinase domain and regulate LRRK2 conformation and function. One helix in COR-B (COR-B Helix) tethers the COR-B domain to the αC helix of the kinase domain and faces its activation loop, while the C-terminal helix (Ct-Helix) extends from the WD40 domain and interacts with both kinase lobes. The Ct-Helix and the N-terminus of the COR-B Helix create a “cap” that regulates the N-lobe of the kinase domain. Our analyses reveal allosteric sites for pharmacological intervention and confirm the kinase domain as the central hub for conformational control.
Structural and functional brain alterations in patients with myasthenia gravis

Abstract Myasthenia gravis is an autoimmune disease affecting neuromuscular transmission and causing skeletal muscle weakness. Additionally, systemic inflammation, cognitive deficits and autonomic dysfunction have been described. However, little is known about myasthenia gravis-related reorganization of the brain. In this study, we thus investigated the structural and functional brain changes in myasthenia gravis patients. Eleven myasthenia gravis patients (age: 70.64 ± 9.27; 11 males) were compared to age-, sex- and education-matched healthy controls (age: 70.18 ± 8.98; 11 males). Most of the patients (n = 10, 0.91%) received cholinesterase inhibitors. Structural brain changes were determined by applying voxel-based morphometry using high-resolution T1-weighted sequences. Functional brain changes were assessed with a neuropsychological test battery (including attention, memory and executive functions), a spatial orientation task and brain-derived neurotrophic factor blood levels. Myasthenia gravis patients showed significant grey matter volume reductions in the cingulate gyrus, in the inferior parietal lobe and in the fusiform gyrus. Furthermore, myasthenia gravis patients showed significantly lower performance in executive functions, working memory (Spatial Span, P = 0.034, d = 1.466), verbal episodic memory (P = 0.003, d = 1.468) and somatosensory-related spatial orientation (Triangle Completion Test, P = 0.003, d = 1.200). Additionally, serum brain-derived neurotrophic factor levels were significantly higher in myasthenia gravis patients (P = 0.001, d = 2.040). Our results indicate that myasthenia gravis is associated with structural and functional brain alterations. Especially the grey matter volume changes in the cingulate gyrus and the inferior parietal lobe could be associated with cognitive deficits in memory and executive functions. Furthermore, deficits in somatosensory-related spatial orientation could be associated with the lower volumes in the inferior parietal lobe. Future research is needed to replicate these findings independently in a larger sample and to investigate the underlying mechanisms in more detail.
Persistent fecal occult blood due to the small intestinal metastasis of pleomorphic lung carcinoma

Abstract The gastrointestinal tract is one of the locations that lung cancers cause metastasis. A 70-year-old male underwent right lower lobectomy while presenting fecal occult blood with a preoperative colonoscopy showing colon polyps as the cause. The pathological diagnosis was pleomorphic carcinoma of the lung, with stage pT3N0M0. Seven months after the lung surgery, the patient presented with sudden-onset abdominal pain and severe anemia. Computed tomography scanning revealed a large mass in the abdominal cavity, and subsequent intestinal endoscopy demonstrated jejunum tumors. Partial jejunum resection was successfully performed. The patient developed multiple peritoneal nodules suggesting metastatic tumors but well responded to an immune checkpoint inhibitor. It can be challenging to diagnose gastrointestinal metastasis in routine radiography; therefore, endoscopic examination, including the small intestine, might be an important option when a lung cancer patient with advanced clinical stage presents with abdominal symptoms, including fecal occult blood.
“Who am I going to stay with? Who will accept me?”: family‐level domains influencing HIV care engagement among disengaged adolescents in Kenya

Adolescents living with HIV (ALHIV, ages 10–19) have developmentally specific needs in care, and have lower retention compared to other age groups. Family‐level contexts may be critical to adolescent HIV outcomes, but have often been overlooked. We investigated family‐level factors underlying disengagement and supporting re‐engagement among adolescents disengaged from HIV care.