Miracle-dz/UniFAR-FTUs huggingface dataset:
Predictive and prognostic biomarkers with therapeutic targets in colorectal cancer: A 2021 update on current development, evidence, and recommendation

Although therapeutically actionable molecular alterations are widely distributed across many cancer types, only a handful of them show evidence of clinical utility and are recommended for routine clinical practice in the management of cancers of colon and rectum (CRC). This 2021 update aims to provide a succinct summary on the use of prognostic and/or predictive biomarkers (expanded RAS, BRAF, microsatellite-high [MSI-H] or deficient mismatch repair [dMMR], neurotrophic tyrosine receptor kinase [NTRK] fusion genes, and human epidermal growth factor receptor type II [HER2] gene amplification) associated with CRC. Therapeutic implications of each relevant predictive or prognostic biomarker for patients with CRC are described, along with discussion on new developments on (1) biomarker-driven therapies such as testing of BRAF, MLH1 promoter methylation and MMR germline genes in differentiating sporadic CRC or hereditary conditions such as Lynch syndrome; (2) first-line use of immune checkpoint inhibitors in metastatic CRC; (3) risk stratification and therapy selection based on primary tumor location (left-sided vs. right-sided colon cancer); (3) atypical BRAF mutations; (4) use of EGFR directed therapy in the perioperative oligometastatic disease setting; (5) re-challenge of EGFR directed therapy and (6) personalizing therapy of fluoropyrimidine and irinotecan based on new evidence in pharmacogenomic testing. Data are collected and analyzed from available systematic reviews and meta-analyses of treatments with known therapeutic targets in CRC, which may be associated with predictive and/or prognostic biomarkers. Discussions are presented in an application-based format, with goal to empower pharmacists or other clinicians to gain awareness and understanding in biomarker-driven cancer therapy issues.
Incident obstructive lung disease and mortality among people with HIV and a history of injecting drugs

Supplemental Digital Content is available in the text Objective: People with HIV (PWH) experience increased prevalence of obstructive lung disease (OLD), regardless of greater observed smoking behaviors. We investigated whether the effect of incident OLD on mortality differed by HIV and HIV viral suppression among persons who inject drugs (PWID) and report smoking history. Design: ALIVE is a longitudinal, observational cohort study of HIV-positive and seronegative PWID. This analysis included participants who had at least one spirometry measure to assess OLD between 2007 and 2016, excluding those who never smoked (5%, n = 62) or had baseline OLD (17%, n = 269). Methods: Incident OLD occurred when the first prebronchodilator forced expiratory volume in one second (FEV1)/forced vital capacity (FVC) less than 0.70 during follow-up. The effect of incident OLD on all-cause mortality was estimated in PWH and seronegative participants using inverse-probability-of-treatment-weighted marginal structural models controlling for baseline (age, race, sex, calendar year, smoking pack-years) and time-varying (smoking intensity, viral suppression, and calendar time) confounders. Results: Among 1204 participants, 269 (22.3%) and 157 (13.0%) experienced incident OLD and death, respectively, over a median of five person-years of follow-up. There was no effect of OLD on mortality among seronegative participants [hazard ratio = 0.84, 95% confidence interval (CI): 0.47–1.48]; however, PWH diagnosed with OLD experienced an increased mortality risk (hazard ratio = 1.71, 95% CI: 1.04–2.80) during follow-up. HIV viral suppression did not confound or modify the effect of OLD on mortality among PWH. Conclusion: There was an apparent effect of OLD on all-cause mortality irrespective of viral suppression among PWH but not among seronegative persons, after accounting for baseline and time-varying confounders. These results highlight the need for enhanced screening and management of OLD among PWH.
We Speak a Different Language: End-of-Life and Bereavement Experiences of Older Lesbian, Gay, and Bisexual Women Who Have Lost a Spouse or Partner

We examine the end-of-life (EOL) experiences, communications, and grief support during and after their loved one’s death of older lesbian, gay, and bisexual women (LGB) ages 60 to 85 who have lost a spouse or partner. Queer gerontology was used as a theoretical framework, and descriptive qualitative analytical methods were used to discern themes. Through semi-structured interviews with a purposive sample of 16 participants, we identified two main themes: Gathering the Women and Compassionate Care. Although older LGB women may have some similar support needs as non-LGB adults, other needs are distinct but often unmet. While our participants’ interactions with health care professionals were overtly positive, there was often a lack of communication about grief resources, including lesbian and women-specific grief groups. Overall researchers, policymakers, and practitioners should be mindful of the importance of fully integrating and including populations into their care practices to avoid creating systems of superficial tolerance.
Genetic effect of MTHFR C677T, A1298C, and A1793G polymorphisms on the age at onset, plasma homocysteine, and white matter lesions in Alzheimer's disease in the Chinese population

Background: Three polymorphisms in the Methylenetetrahydrofolate reductase (MTHFR) gene (C677T, A1298C, and A1793G) were reported associated with AD. However, their genotype distributions and associations with age at onset (AAO), homocysteine, and white matter lesions (WML) were unclear in the Chinese AD population. Method: We determined the presence of C677T, A1298C, and A1793G polymorphisms in the MTHFR gene using Sanger sequencing in a Chinese cohort comprising 721 AD patients (318 early-onset AD patients (EOAD) and 403 late-onset AD patients (LOAD)) and 365 elderly controls. Additionally, the homocysteine level and WML were evaluated in 121 AD patients. Results: The frequency of allele T of C677T polymorphism was significantly higher in AD patients than in controls (P = 0.040), while no statistical difference was observed in A1298C and A1793G (P > 0.05). Besides, genotype distributions of C677T and A1298C polymorphisms statistically varied between AD patients and controls (P = 0.021, P = 0.012). Moreover, the AAO was significantly lower in CT/TT (C677T) genotypes carriers (P = 0.042) and higher in AC/CC (A1298C) and AG/GG (A1793G) genotypes carriers (P = 0.034, P = 0.009) in patients with LOAD. We also found that patients with CT/TT (C677T) genotypes were prone to present an increased homocysteine level (P = 0.036) and higher Fazekas score (P = 0.024). In comparison, patients with AG/GG genotypes (A1793G) had a significantly lower Fazekas score (P = 0.013). Conclusions: The genotype distributions of C677T and A1298C polymorphisms are associated with AD in the Chinese population. Moreover, AD patients with C677T polymorphism are prone to present an earlier onset, higher homocysteine level, and more severe WML.
Effect of Tibial Tunnel Placement Using the Lateral Meniscus as a Landmark on Clinical Outcomes of Anatomic Single-Bundle Anterior Cruciate Ligament Reconstruction

Background: It remains unclear if use of the lateral meniscus anterior horn (LMAH) as a landmark will produce consistent tunnel positions in the anteroposterior (AP) distance across the tibial plateau. Purpose: To evaluate the AP location of anterior cruciate ligament (ACL) reconstruction tibial tunnels utilizing the LMAH as an intra-articular landmark and to examine how tunnel placement affects knee stability and clinical outcomes. Study Design: Cohort study; Level of evidence, 3. Methods: A retrospective review was conducted of 98 patients who underwent primary ACL reconstruction with quadrupled hamstring tendon autografts between March 2013 and June 2017. Patients with unilateral ACL injuries and a minimum follow-up of 2 years were included in the study. All guide pins for the tibial tunnel were placed using the posterior border of the LMAH as an intra-articular landmark. Guide pins were evaluated with the Bernard-Hertel grid in the femur and the Stäubli-Rauschning method in the tibia. Patients were divided by the radiographic location of the articular entry point of the guide pin with relation to the anterior 40% of the tibial plateau. Outcomes were evaluated by the Marx Activity Scale and International Knee Documentation Committee (IKDC) form. Anterior knee laxity was evaluated using a KT-1000 arthrometer and graded with the objective portion of the IKDC form. Rotational stability was evaluated using the pivot-shift test. Results: A total of 60 patients were available for follow-up at a mean 28.6 months. The overall percentage of AP placement of the tibial tunnel was 39.3% ± 3.8% (mean ± SD; range, 31%-47%). Side-to-side difference of anterior knee laxity was significantly lower in the anterior group than the posterior group (1.2 ± 1.1 mm vs 2.5 ± 1.3 mm; P < .001; r = 0.51). The percentage of AP placement of the tibial tunnel demonstrated a positive medium correlation with side-to-side difference of anterior knee laxity as measured by a KT-1000 arthrometer (r = 0.430; P < .001). The anterior group reported significantly better distribution of IKDC grading as compared with the posterior group (26 grade A and 6 grade B vs 15 grade A and 13 grade B; P = .043; V = 0.297). The pivot-shift test results and outcome scores showed no significant differences between the groups. Conclusion: Using the posterior border of the LMAH as an intraoperative landmark yields a wide range of tibial tunnel locations along the tibial plateau, with anterior placement of the tibial tunnel leading toward improved anterior knee stability.
Backyard poultry cases in UK small animal practices: Demographics, health conditions and pharmaceutical prescriptions

Abstract Background: Backyard poultry ownership is of keen interest in the United Kingdom. However, despite this, little is known about veterinary care engagement and outcomes of visits in this group of species. Methods: This study described and characterised veterinary practice‐visiting backyard poultry, utilising electronic health record data supplied by veterinary practices voluntarily participating in the Small Animal Veterinary Surveillance Network between 1st April 2014 and 31st March 2019. Results: In total, 4424 recorded poultry consultations originating from 197 veterinary practices (352 sites) were summarised. Chicken consultation (n = 3740) peak incidence was in early summer (April‐June), relative to all recorded species. More chickens resided in rural (incident rate ratio = 2.5, confidence interval [CI] 2.3–2.6, p <0.001) or less deprived areas. Non‐specific clinical signs were commonly recorded (17.6% of chicken consultations, CI 15.9–19.2), as were those indicative of advanced disease. This latter finding was reflected in prescribed management strategies, with euthanasia comprising 29.8% (CI 27.0–32.6) of consultations. Antimicrobials were commonly prescribed (33.0% of consultations, CI 29.8–36.2), 43.8% of which included antimicrobials considered ‘highest priority critically important’ by the World Health Organisation. Conclusion: Our findings indicate a need to tailor antimicrobial prescription guidance to the backyard poultry setting. In addition, late presentation of disease, vague clinical descriptions in clinical narratives and high euthanasia rates show that disease identification, management and knowledge of poultry health and welfare among owners and veterinary surgeons can be improved.
Pain Trends Among American Adults, 2002–2018: Patterns, Disparities, and Correlates

Determining long-term trends in chronic pain prevalence is critical for evaluating and shaping U.S. health policies, but little research has examined such trends. This study (1) provides estimates of pain trends among U.S. adults across major population groups; (2) tests whether sociodemographic disparities in pain have widened or narrowed over time; and (3) examines socioeconomic, behavioral, psychological, and medical correlates of pain trends. Regression and decomposition analyses of joint, low back, neck, facial/jaw pain, and headache/migraine using the 2002–2018 National Health Interview Survey for adults aged 25–84 (N = 441,707) assess the trends and their correlates. We find extensive escalation of pain prevalence in all population subgroups: overall, reports of pain in at least one site increased by 10%, representing an additional 10.5 million adults experiencing pain. Socioeconomic disparities in pain are widening over time, and psychological distress and health behaviors are among the salient correlates of the trends. This study thus comprehensively documents rising pain prevalence among Americans across the adult life span and highlights socioeconomic, behavioral, and psychological factors as important correlates of the trends. Chronic pain is an important dimension of population health, and demographic research should include it when studying health and health disparities.
Effect of Aprepitant for the Prevention of Chemotherapy-Induced Nausea and Vomiting in Women

Key Points Question Is prophylactic aprepitant therapy combined with palonosetron and dexamethasone effective in preventing nausea and vomiting in women receiving moderately emetogenic chemotherapy? Findings In this randomized phase 3 clinical trial that included 248 women younger than 50 years with no or little alcohol use, the complete response rate in the overall phase for chemotherapy-induced nausea and vomiting was 87% in the aprepitant group vs 67% in the control group. The overall complete response rate was significantly higher in the aprepitant group vs the control group. Meaning Adding aprepitant to palonosetron and dexamethasone was effective in reducing nausea and vomiting for women who received moderately emetogenic chemotherapy.
Gain‐of‐Function Lrp5 Mutation Improves Bone Mass and Strength and Delays Hyperglycemia in a Mouse Model of Insulin‐Deficient Diabetes

High fracture rate and high circulating levels of the Wnt inhibitor, sclerostin, have been reported in diabetic patients. We studied the effects of Wnt signaling activation on bone health in a mouse model of insulin‐deficient diabetes. We introduced the sclerostin‐resistant Lrp5A214V mutation, associated with high bone mass, in mice carrying the Ins2Akita mutation (Akita), which results in loss of beta cells, insulin deficiency, and diabetes in males. Akita mice accrue less trabecular bone mass with age relative to wild type (WT). Double heterozygous Lrp5A214V/Akita mutants have high trabecular bone mass and cortical thickness relative to WT animals, as do Lrp5A214V single mutants. Likewise, the Lrp5A214V mutation prevents deterioration of biomechanical properties occurring in Akita mice. Notably, Lrp5A214V/Akita mice develop fasting hyperglycemia and glucose intolerance with a delay relative to Akita mice (7 to 8 vs. 5 to 6 weeks, respectively), despite lack of insulin production in both groups by 6 weeks of age. Although insulin sensitivity is partially preserved in double heterozygous Lrp5A214V/Akita relative to Akita mutants up to 30 weeks of age, insulin‐dependent phosphorylated protein kinase B (pAKT) activation in vitro is not altered by the Lrp5A214V mutation. Although white adipose tissue depots are equally reduced in both compound and Akita mice, the Lrp5A214V mutation prevents brown adipose tissue whitening that occurs in Akita mice. Thus, hyperactivation of Lrp5‐dependent signaling fully protects bone mass and strength in prolonged hyperglycemia and improves peripheral glucose metabolism in an insulin independent manner. Wnt signaling activation represents an ideal therapeutic approach for diabetic patients at high risk of fracture. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).
Regenerative replacement of neural cells for treatment of spinal cord injury

ABSTRACT Introduction: Traumatic Spinal Cord Injury (SCI) results from primary physical injury to the spinal cord, which initiates a secondary cascade of neural cell death. Current therapeutic approaches can attenuate the consequences of the primary and secondary events, but do not address the degenerative aspects of SCI. Transplantation of neural stem/progenitor cells (NPCs) for the replacement of the lost/damaged neural cells is suggested here as a regenerative approach that is complementary to current therapeutics. Areas Covered: This review addresses how neurons, oligodendrocytes, and astrocytes are impacted by traumatic SCI, and how current research in regenerative-NPC therapeutics aims to restore their functionality. Methods used to enhance graft survival, as well as bias progenitor cells towards neuronal, oligodendrogenic, and astroglia lineages are discussed. Expert Opinion: Despite an NPC’s ability to differentiate into neurons, oligodendrocytes, and astrocytes in the transplant environment, their potential therapeutic efficacy requires further optimization prior to translation into the clinic. Considering the temporospatial identity of NPCs could promote neural repair in region specific injuries throughout the spinal cord. Moreover, understanding which cells are targeted by NPC-derived myelinating cells can help restore physiologically-relevant myelin patterns. Finally, the duality of astrocytes is discussed, outlining their context-dependent importance in the treatment of SCI.
Osteoporosis is under recognized and undertreated in adult spinal deformity patients.

Background Adult spinal deformity (ASD) patients may have osteoporosis, predisposing them to an increased risk for surgical complications. Prior studies have demonstrated that treating osteoporosis improves surgical outcomes. In this study we determine the prevalence of osteoporosis in ASD patients undergoing long spinal fusions and the rate at which osteoporosis is treated. Methods ASD patients who frequented either of two major academic medical centers from 2010 through 2019 were studied. All study participants were at least 40 years of age and endured a spinal fusion of at least seven vertebral levels. Medical records were explored for a diagnosis of osteoporosis via ICD-10 code and, if present, whether pharmacological treatment was prescribed. T-tests and chi-squared analyses were used to determine statistical significance. Results Three hundred ninety-nine patients matched the study's inclusion criteria. Among this group, 131 patients (32.8%) had been diagnosed with osteoporosis prior to surgery. With a mean age of 66.4 years, osteoporotic patients were on average three years older than non-osteoporotic (P=0.002) and more likely to be female (74.8% vs. 61.9%; P=0.01). At the time of surgery, 34.4% of osteoporotic patients were receiving pharmacological treatment. Although not statistically significant, women were more likely to receive medical treatment than men (P=0.07). Conclusions The prevalence of osteoporosis in ASD patients undergoing a long spinal fusion is substantially higher than that of the general population. Surgeons should have a low threshold for bone density testing in ASD patients. With only about one-third of osteoporotic patients treated, there is a classic "missed opportunity" in this population.
Efficacy and safety of methylprednisolone against acute respiratory distress syndrome

Supplemental Digital Content is available in the text Abstract Background: Acute respiratory distress syndrome (ARDS) is caused by an inflammatory injury to the lung. Dysregulated inflammation is the cardinal feature of ARDS. Methylprednisolone is an option for treating ARDS. However, the benefits and adverse effects of methylprednisolone have not been well assessed in patients with ARDS. This study aimed to evaluate the efficacy and safety of methylprednisolone against ARDS. Material and methods: The electronic database of Embase, PubMed, the Cochrane Library, CNKI, and Wanfang were searched, and randomized controlled trials (RCTs) reporting the efficacy and safety of methylprednisolone for ARDS were included. Revman 5.3 and Stata 15.0 were used to conduct the analysis. The fixed-effects model was used to calculate summary odds ratios (ORs) and 95% confidence interval (CIs). Results: Ten RCTs studies involving 692 patients with ARDS. The summary results demonstrated that, compared with placebo, methylprednisolone had a statistically significant effect on mortality (OR = 0.64; 95% CI: 0.43–0.95, I2 = 42%); the time of mechanical ventilation (MD) = –2.70, 95% CI: –3.31 to –2.10; I2 = 0%) in patients with ARDS, but it was not associated with increased rates of adverse events (OR = 0.80; 95% CI: 0.34–1.86; I2 = 58%). Conclusions: This systematic review and meta-analysis demonstrated that Methylprednisolone is safe against ARDS. It may reduce mortality and shorten the time of mechanical ventilation. However, well-designed and large-sample studies were required to fully characterize the efficacy and safety of methylprednisolone against ARDS.
The school policy, social, and physical environment and change in adolescent physical activity: An exploratory analysis using the LASSO

Purpose We examined the association between the school policy, social and physical environment and change in adolescent physical activity (PA) and explored how sex and socioeconomic status modified potential associations. Methods Data from the GoActive study were used for these analyses. Participants were adolescents (n = 1765, mean age±SD 13.2±0.4y) from the East of England, UK. Change in longitudinal accelerometer assessed moderate-to-vigorous physical activity (MVPA) was the outcome. School policy, social and physical environment features (n = 267) were exposures. The least absolute shrinkage and selection operator variable selection method (LASSO) was used to determine exposures most relevant to the outcome. Exposures selected by the LASSO were added to a multiple linear regression model with estimates of change in min/day of MVPA per 1-unit change in each exposure reported. Post-hoc analyses, exploring associations between change in variables selected by the LASSO and change in MVPA, were undertaken to further explain findings. Findings No school policy or physical environment features were selected by the LASSO as predictors of change in MVPA. The LASSO selected two school social environment variables (participants asking a friend to do physical activity; friend asking a participant to do physical activity) as potential predictors of change in MVPA but no significant associations were found in subsequent linear regression models for all participants (β [95%CI] -1.01 [-2.73;0.71] and 0.65 [-2.17;0.87] min/day respectively). In the post-hoc analyses, for every unit increase in change in participants asking a friend to do PA and change in a friend asking participants to do PA, an increase in MVPA of 2.78 (1.55;4.02) and 1.80 (0.48;3.11) min/day was predicted respectively. Conclusions The school social environment is associated with PA during adolescence. Further exploration of how friendships during adolescence may be leveraged to support effective PA promotion in schools is warranted.