Miracle-dz/UniFAR-FTUs huggingface dataset:
Five-Year Outcomes After Transforaminal Endoscopic Foraminotomy and Discectomy for Soft and Calcified Thoracic Disc Herniations

ABSTRACT Background: The aim of this study was to evaluate the safety and long-term clinical outcomes of transforaminal full endoscopic discectomy and foraminotomy performed with manual reamers under local anesthesia on soft and calcified herniated discs in the mid and lower thoracic spine. Methods: Postoperative pain relief was self-evaluated by 16 patients using a visual analog scale (VAS) and Oswestry Disability Index (ODI). Patients were scored at 6, 12, 24, and 60 months after surgery. Results: Significant pain reduction of more than 50% in the VAS score was achieved in 15 out of 16 patients at all review points throughout this study. Similarly, a decrease of more than 50% in ODI scores was achieved in 15 out of 16 patients in all 4 review points. There were no surgical complications. Good postoperative results were achieved in patients regardless of the consistency of the disc herniation. Conclusions: Transforaminal full endoscopic discectomy and foraminotomy with manual reamers performed under local anesthesia produces sustained reduction in pain and improves functionality in patients with mid and lower thoracic spine soft and calcified disc herniations. The surgery is safe and straightforward to perform with the correct training. Level of Evidence: 4. Clinical Relevance: Thoracic transforaminal endoscopic discectomy and foraminotomy, performed in TIVA, may be a useful adjunct for treatment of patients with soft and calcified disc herniations in thoracic spine.
Synthesis of a self-healable and pH responsive hydrogel based on an ionic polymer/clay nanocomposite

This investigation reports the preparation of a pH responsive self-healing nanocomposite hydrogel based on the in situ polymerization of 2-(acryloyloxy)ethyl trimethylammonium chloride and acrylic acid using N,N′-methylenebisacrylamide as a crosslinker and ammonium persulfate (APS) as a thermal initiator in the presence of soluble starch and organically modified montmorillonite (OMMT). The hydrogel was characterized using FTIR, SEM and TEM analyses. The influence of different parameters in swelling was investigated. The self-healing ability of the hydrogel was measured in different pH media and it was observed that it can show self-healing ability in physiological pH (pH = 7.4), in acidic pH (pH = 1.2) and in saline solution. This developed hydrogel showed excellent swelling ratio, mechanical strength, and elasticity. The hydrogel exhibited modulus values (G′, G′′) in the range of 102 Pa.
Synthesis, Characterization, and Photopolymerization of Polyisobutylene Phenol (Meth)acrylate Macromers

Polyisobutylene (PIB) phenol (meth)acrylates were produced by reacting di- or triphenol-terminated PIB with (meth)acryloyl chloride. 1H NMR, GPC, and MALDI-TOF MS characterization showed that meth(acrylate) end-functionality was 2 and 3, respectively, and that targeted molecular weights and relatively low polydispersities were achieved. Comparative aliphatic PIB triol triacrylate was prepared by end-quenching living polyisobutylene with 4-phenoxy-1-butyl acrylate. A photopolymerization study of PIB diphenol di(meth)acrylates with Mn about 3000 g/mol, PIB triphenol tri(meth)acrylates with Mn about 4000 and 10 000 g/mol, and control aliphatic PIB triol triacrylate with Mn about 10 000 g/mol was conducted. Darocur 1173 and Irgacure 819 and 651 photoinitiators were studied, and FTIR reaction monitoring showed that Darocur 1173 afforded the highest rate of photopolymerization and final conversion, apparently due to its higher solubility in PIB. At Mn ≅ 4000 g/mol, the rate of photopolymerization and conversion.
Association between nutrition delivery, modified Nutrition Risk in Critically Ill score, and 28-day mortality.

BACKGROUND Nutrition delivery, is a key component in the management of critical illness. Traditional scoring systems are inadequate in the intensive care unit (ICU), as patients are sedated. Our study examines the associations between calorie and protein adequacy, 28-day mortality, and modified Nutrition Risk in Critically Ill (mNUTRIC) score and identify at-risk ICU patients who may benefit more from nutrition intervention. METHODS Prospective observational study of adults admitted for >24h to the ICU of a tertiary care hospital during a period of 7 months. Data were collected on nutrition delivery, mNUTRIC score, use of mechanical ventilation, and ICU/hospital length of stay (LOS). Multivariate logistic regression analysis was done with 28-day mortality as the primary outcome. RESULTS Two hundred forty-eight patients were recruited for the study with 60% male, 40% female, mean age 60.8 ± 14.7, and body mass index of 24.2 ± 4.8. Patients with inadequate calorie and protein delivery had significantly higher 28-day mortality than those with adequate provision (P=.032 and P =. 017). In bivariate logistic regression analysis, mNUTRIC score (odds ratio [OR], 1.802; 95% CI, 1.042-3.117; P = .035) and adequacy of energy (OR, 1.92) and protein (OR, 2.49) correlate with 28-day mortality. The Kaplan-Meier survival curve showed a survival benefit in the ≥80% energy and protein group among the total patients and was also significantly associated with lower hospital and ICU LOS, even after matching (log-rank test, P < 0.001). CONCLUSION Adequacy of energy and protein to ≥80% may shorten ICU/hospital LOS and reduce 28-day mortality among both high and low nutrition risk patients.
Attitudes and perceptions of next-of-kin/loved ones toward end-of-life HIV cure-related research: A qualitative focus group study in Southern California

As end-of-life (EOL) HIV cure-related research expands, understanding perspectives of participants’ next-of-kin (NOK) is critical to maintaining ethical study conduct. We conducted two small focus groups and two one-on-one interviews using focus group guides with the NOK of Last Gift study participants at the University of California, San Diego (UCSD). Participating NOK included six individuals (n = 5 male and n = 1 female), including a grandmother, grandfather, partner, spouse, and two close friends. Researchers double-coded the transcripts manually for overarching themes and sub-themes using an inductive approach. We identified six key themes: 1) NOK had an accurate, positive understanding of the Last Gift clinical study; 2) NOK felt the study was conducted ethically; 3) Perceived benefits for NOK included support navigating the dying/grieving process and personal growth; 4) Perceived drawbacks included increased sadness, emotional stress, conflicted wishes between NOK and study participants, and concerns around potential invasiveness of study procedures at the EOL; 5) NOK expressed pride in loved ones’ altruism; and 6) NOK provided suggestions to improve the Last Gift study, including better communication between staff and themselves. These findings provide a framework for ethical implementation of future EOL HIV cure-related research involving NOK.
3D Printing of Strontium Silicate Microcylinder‐Containing Multicellular Biomaterial Inks for Vascularized Skin Regeneration

The reconstruction of dermal blood vessels is essential for skin regeneration process. However, the lack of vascular structure, insufficient angiogenesis induction, and ineffective graft‐host anastomosis of the existing skin substitutes are major bottle‐necks for permanent skin replacement in tissue engineering. In this study, the uniform strontium silicate (SS) microcylinders are successfully synthesized and integrated into the biomaterial ink to serve as stable cell‐induced factors for angiogenesis, and then a functional skin substitute based on a vascularization‐induced biomimetic multicellular system is prepared via a “cell‐writing” bioprinting technology. With an unprecedented combination of vascularized skin‐mimicking structure and vascularization‐induced function, the SS‐containing multicellular system exhibits outstanding angiogenic activity both in vitro and in vivo. As a result, the bioprinted skin substitutes significantly accelerate the healing of both acute and chronic wounds by promoting the graft‐host integration and vascularized skin regeneration in three animal models. Therefore, the study provides a referable strategy to fabricate biomimetic multicellular constructs with angiogenesis‐induced function for regeneration of vascularized complex and hierarchical tissues.
Mutation spectrum of hereditary myopathies in Turkish patients and novel variants

Hereditary myopathies are a heterogeneous disorder known to be associated with more than 100 genes. Although hereditary myopathy subgroups can be partially described with traditional methods such as muscle biopsy, next‐generation sequencing (NGS) is essential to reveal the disease's underlying genetic etiology and molecular mechanisms. In this study, we performed clinical exome sequencing or whole‐exome sequencing (CES/WES) in 20 unrelated Turkish patients. Thirteen pathogenic or likely pathogenic variants, including five novel variantswere detected in the 16 known hereditary myopathy genes. We achieved a high rate of diagnosis (65%) compared to previous studies. The most common condition noticed was limb‐girdle muscular dystrophy (LGMD), which should not be ignored in patients diagnosed with myopathy. CES or WES provides a certain molecular diagnosis from a broad perspective to demonstrate underlying genetic causes in heterogeneous disorders. Therefore, exome sequencing offers a higher and more complete diagnosis than the gene panel.
Motivations, barriers, and communication recommendations for promoting face coverings during the COVID-19 pandemic: Survey findings from a diverse sample

State and local health departments have been tasked with promoting the use of face coverings to decrease the spread of COVID-19 in their respective communities. However, little is known about motivations and barriers to wearing face coverings in the context of COVID-19 prevention, particularly among communities of color who are at an increased risk of serious illness from the disease. The purpose of this study was to identify common motivations and barriers to face covering use, as well as explore perceptions of messages encouraging the use of face coverings among a racially and ethnically diverse sample. A survey was distributed electronically to North Carolina (NC) residents through NC Department of Health and Human Services listservs in July 2020. Participants self-categorized as Latino/a (33.5%), Black (39.1%), or white or another race (27.5%). The most commonly endorsed motivations for wearing face coverings were to avoid spreading COVID-19 (77%), as well as to protect people who are vulnerable (76%) and one’s community (72%). Being uncomfortable (40%) was the most commonly endorsed barrier. Messages that included a clear request (ex. please wear a face covering) and a direct benefit (ex. keep community safe) were more commonly endorsed than those that did not. Commonly endorsed motivations, behaviors, and messages differed by race and ethnicity. Increased attention to message content, message structure, and access to information and resources may aid local officials in increasing consistent use of face coverings.
Habitual flavonoid intake and ischemic stroke incidence in the Danish Diet, Cancer, and Health Cohort

ABSTRACT Background Flavonoid-rich foods have antiinflammatory, antiatherogenic, and antithrombotic properties that may contribute to a lower risk of ischemic stroke. Objectives We aimed to investigate the relationship between habitual flavonoid consumption and incidence of ischemic stroke in participants from the Danish Diet, Cancer and Health Study. Design In this prospective cohort study, 55,169 Danish residents without a prior ischemic stroke [median (IQR) age at enrolment of 56 y (52–60)], were followed for 21 y (20–22). We used Phenol-Explorer to estimate flavonoid intake from food frequency questionnaires obtained at study entry. Incident cases of ischemic stroke were identified from Danish nationwide registries and restricted cubic splines in Cox proportional hazards models were used to investigate relationships with flavonoid intake. Results During follow-up, 4237 individuals experienced an ischemic stroke. Compared with participants in Q1 and after multivariable adjustment for demographics and lifestyle factors, those in Q5—for intake of total flavonoids, flavonols, and flavanol oligo + polymers—had a 12% [HR (95% CI): 0.88 (0.81, 0.96)], 10% [0.90 (0.82, 0.98)], and 18% [0.82 (0.75, 0.89)] lower risk of ischemic stroke incidence, respectively. Multivariable (demographic and lifestyle) adjusted associations for anthocyanins and flavones with risk of ischemic stroke were not linear, with moderate but not higher intakes associated with lower risk [anthocyanins Q3 vs. Q1 HR (95% CI): 0.85 (0.79, 0.93); flavones: 0.90 (0.84, 0.97)]. Following additional adjustment for dietary confounders, similar point estimates were observed; however, significance was only retained for anthocyanins and flavanol oligo + polymers [anthocyanins Q3 vs. Q1 HR (95% CI): 0.86 (0.79, 0.94); flavanol oligo + polymers Q5 vs. Q1 0.86 (0.78, 0.94)]. Conclusions These findings suggest that moderate habitual consumption of healthy flavonoid-rich foods is associated with a lower risk of ischemic stroke and further investigation is therefore warranted.
The association of maternal gestational hyperglycemia with breastfeeding duration and markers of milk production.

BACKGROUND Previous studies focusing on the association between gestational diabetes and breastfeeding duration have been inconclusive. OBJECTIVES We aimed to determine whether maternal gestational hyperglycemia is associated with the duration of breastfeeding and the concentrations of markers linked to breastmilk production. METHODS Data from the prospective, multiethnic Growing Up in Singapore Towards Healthy Outcomes study were used to assess the association of fasting plasma glucose (FPG) and 2-h postglucose challenge (2hPG) measured at 26-28 wk of gestation with duration of breastfeeding and concentrations of protein, lactose, citrate, sodium, potassium, and zinc in breastmilk 3 wk postpartum. RESULTS Of the 1035 participants, 5.2% and 9.5% had elevated FPG and 2hPG, respectively, consistent with a diagnosis of gestational diabetes mellitus based on International Association of Diabetes and Pregnancy Study Groups criteria. FPG ≥5.1 mmol/L was associated with a crude reduction in median breastfeeding duration of 2.3 mo. In a model adjusted for maternal prepregnancy BMI and intention to breastfeed, FPG ≥5.1 mmol/L predicted earlier termination of any breastfeeding (adjusted HR: 1.47; 95% CI: 1.04, 2.08) but not full breastfeeding (adjusted HR: 1.08; 0.76, 1.55). 2hPG ≥8.5 mmol/L was not significantly associated with the durations of any (adjusted HR: 0.86; 95% CI: 0.62, 1.19) or full (adjusted HR: 0.85; 95% CI: 0.62, 1.18) breastfeeding. Maternal FPG was significantly and positively associated with breastmilk sodium (adjusted coefficient: 1.28; 95% CI: 1.08, 1.51) and sodium-to-potassium ratio (adjusted coefficient: 1.29; 95% CI: 1.08, 1.54) but not with other measured breastmilk components. CONCLUSIONS Women with FPG ≥5.1 mmol/L during pregnancy breastfeed for a shorter duration. Future work involving measurement of milk production is needed to determine whether low milk production predicts breastfeeding duration among women with elevated FPG. This trial was registered at www.clinicaltrials. gov as NCT01174875.
GCN4 Regulates Secondary Metabolism through Activation of Antioxidant Gene Expression under Nitrogen Limitation Conditions in Ganoderma lucidum

Nitrogen has been widely reported to regulate secondary metabolism in fungi. Our study assessed the specific nitrogen regulatory mechanisms in Ganoderma lucidum. ABSTRACT Nitrogen limitation has been widely reported to affect the growth and development of fungi, and the transcription factor GCN4 (general control nonderepressible 4) is involved in nitrogen restriction. Here, we found that nitrogen limitation highly induced the expression of GCN4 and promoted the synthesis of ganoderic acid (GA), an important secondary metabolite in Ganoderma lucidum. The activated GCN4 is involved in regulating GA biosynthesis. In addition, the accumulation of reactive oxygen species (ROS) also affects the synthesis of GA under nitrogen restrictions. The silencing of the gcn4 gene led to further accumulation of ROS and increased the content of GA. Further studies found that GCN4 activated the transcription of antioxidant enzyme biosynthesis genes gr, gst2, and cat3 (encoding glutathione reductase, glutathione S-transferase, and catalase, respectively) through direct binding to the promoter of these genes to reduce the ROS accumulation. In conclusion, our study found that GCN4 directly interacts with the ROS signaling pathway to negatively regulate GA biosynthesis under nitrogen-limiting conditions. This provides an essential insight into the understanding of GCN4 transcriptional regulation of the ROS signaling pathway and enriches the knowledge of nitrogen regulation mechanisms in fungal secondary metabolism of G. lucidum. IMPORTANCE Nitrogen has been widely reported to regulate secondary metabolism in fungi. Our study assessed the specific nitrogen regulatory mechanisms in Ganoderma lucidum. We found that GCN4 directly interacts with the ROS signaling pathway to negatively regulate GA biosynthesis under nitrogen-limiting conditions. Our research highlights a novel insight that GCN4, the nitrogen utilization regulator, participates in secondary metabolism through ROS signal regulation. In addition, this also provides a theoretical foundation for exploring the regulation of other physiological processes by GCN4 through ROS in fungi.
Neoadjuvant immunoradiotherapy results in high rate of complete pathological response and clinical to pathological downstaging in locally advanced head and neck squamous cell carcinoma

Background Checkpoint inhibitors targeting programmed death receptor-1 (PD-1) have been tested in the neoadjuvant setting for the treatment of locoregionally advanced head and neck squamous cell carcinoma (HNSCC); however, response rates are modest. We hypothesized that adding stereotactic body radiation therapy (SBRT) to anti-PD-1 would be safe prior to definitive surgical resection and would enhance pathological response compared with historical cohorts of patients with locoregionally advanced HNSCC treated with checkpoint inhibitor alone. Methods The Neoadjuvant Immuno-Radiotherapy Trial was an investigator-initiated single institution phase Ib clinical trial that enrolled patients with previously untreated locally advanced HPV-positive and HPV-negative HNSCC between 2018 and 2019. Eligible patients were treated with neoadjuvant SBRT at a total dose of either 40 Gy in 5 fractions or 24 Gy in 3 fractions, delivered in a 1-week timespan, with or without nivolumab, prior to definitive surgical resection. Patients were then planned for treatment with adjuvant nivolumab for 3 months. The primary safety endpoint was unplanned delay in surgery considered to be at least possibly related to neoadjuvant treatment. The primary efficacy endpoints included pathological complete response (pCR), major pathological response (mPR), and the rate of clinical to pathological downstaging after neoadjuvant treatment. Results Twenty-one patients underwent neoadjuvant treatment, which was well tolerated and did not delay surgery, thus meeting the primary endpoint. Tissue responses were characterized by robust inflammatory infiltrates in the regression bed, plasma cells and cholesterol clefts. Among the entire study group, the mPR and pCR rate was 86% and 67%, respectively. Clinical to pathological downstaging occurred in 90% of the patients treated. Conclusion These data demonstrate that radiation delivered only to the gross tumor volume combined with immunotherapy was safe, resulted in a high rate of mPR and should be further evaluated as a locally focused neoadjuvant therapy for patients with head and neck cancer. Trial registration number This study is registered with clinicaltrials.gov (NCT03247712) and is active, but closed to patient accrual.
Prediction of reproductive function recovery after microsurgical varicocelectomy in men from infertile couples: Clinical and laboratory predictors

The objective was to reveal predictors for fertility recovery after varicocelectomy in subfertile men. This retrospective study recruited 93 men with clinical varicocele and pathozoospermia who underwent microsurgical varicocelectomy. Stepwise discriminant analysis was performed to identify predictors of spontaneous pregnancy (SP) after surgery. ‘Clinically significant improvement’ (CSI) following varicocelectomy was defined as an increase in total progressively motile sperm count (TPMSC) by at least 12.5 million (calculated from WHO‐2010 reference values). 52% of patients showed CSI, and 28% reported SP after surgery. Patients who reported SP (group II), compared to that remained infertile (group I), were younger (27.3 ± 2.9 versus 30.2 ± 4.2 years; p < .01), had less infertility period (24.1 ± 14.0 versus 44.4 ± 32.9 months; p < .05) and had initially higher TPMSC (median (25% −75%) = 34 (11–67) versus 9.5 (0–33) mln; p < . 05). The stepwise discriminant analysis showed that male age (coefficient value = −0.157), total sperm motility (0.024) and postoperative increase in TPMSC (0.010) were the significant predictors of SP. The predictive ability, sensitivity and specificity of the discriminant function were 84%, 87%, 76% respectively. This algorithm can be recommended after varicocelectomy in decision‐making on natural conception or the ART protocols usage.
Identification and validation of novel biomarkers and therapeutics for pulpitis using connectivity mapping.

AIM To create an irreversible pulpitis gene signature from microarray data of healthy and inflamed dental pulps, followed by a bioinformatics approach using connectivity mapping to identify therapeutic compounds that could potentially treat pulpitis. METHODOLOGY The Gene Expression Omnibus (GEO) database, an international public repository of genomics datasets, was searched for human microarray datasets assessing pulpitis. An irreversible pulpitis gene expression signature was generated by differential expression analysis. The statistically significant connectivity map (ssCMap) method was used to identify compounds with a highly correlating gene expression pattern. qPCR was used to validate novel pulpitis genes. An ex vivo pulpitis model was used to test the effects of the compounds identified, and the level of inflammatory cytokines was measured with qPCR, ELISA and multiplex array. Means were compared using the t-test or ANOVA with the level of significance set at p≤0.05. RESULTS Pulpitis gene signatures were created using differential gene expression analysis at cutoff points p=0.0001 and 0.000018. Top upregulated genes were selected as potential pulpitis biomarkers. Among these, IL8, IL6 and MMP9 were previously identified as pulpitis biomarkers. Novel up-regulated genes; chemokine (C-C motif) ligand 21 (CCL21), metallothionein 1H (MT1H) and aquaporin 9 (AQP9) were validated in the pulp tissue of teeth clinically diagnosed with irreversible pulpitis using qPCR. ssCMap analysis identified fluvastatin (Statin) and dequalinium chloride (Quaternary ammonium) as compounds with the strongest correlation to the gene signatures (p=0.0001). Fluvastatin reduced IL8, IL6, CCL21, AQP9 (p<0.001) and MMP9 (p<0.05) in the ex-vivo pulpitis model, while dequalinium chloride reduced AQP9 (p<0.001) but had no significant effect on the other biomarkers. CONCLUSIONS AQP9, MT1H and CCL21 were identified and validated as novel biomarkers for pulpitis. Fluvastatin and dequalinium chloride identified by the ssCMap as potential therapeutics for pulpitis reduced selected pulpitis biomarkers in an ex vivo pulpitis model. In vivo testing of these licensed drugs is warranted.