Miracle-dz/UniFAR-FTUs huggingface dataset:
Retinal changes in diabetic patients without diabetic retinopathy

Purpose. The purpose of this study was to measure retinal vessel caliber and to examine early changes in macular thickness using optical coherence tomography (OCT). We evaluated to what extend vascular caliber and macular thickness differed between patients with type 2 diabetes mellitus without diabetic retinopathy compared with healthy individuals. Methods. 26 diabetic patients without diabetic retinopathy and 26 normal participants without any retinal and optic nerve diseases underwent ophthalmic examination, fundus photography, and OCT imaging. Temporal inferior retinal vessel diameters were measured using OCT. Also, we measured macular thickness in nine ETDRS subfields using Cirrus OCT. Results. The mean age in the diabetic group was 61.5 years and in the control group, 55.5 years. Wider retinal arterioles and venules were found in patients with diabetes compared with healthy subjects (120 µm versus 96 µm, p<0.005 and 137 µm versus 120.5 µm, p value <0.001, respectively). In patients with type 2 diabetes mellitus, central macular thickness was significantly thinner than that of control eyes (243.5 µm versus 269.9 µm, p value <0.001). Conclusions. Our results support the hypothesis that the association between vascular damage and structural changes of the neuroretina is an early indicator of retinal impairment in patients with diabetes without diabetic retinopathy.
Distinct subsets of unmyelinated primary sensory fibers mediate behavioral responses to noxious thermal and mechanical stimuli

Behavioral responses to painful stimuli require peripheral sensory neurons called nociceptors. Electrophysiological studies show that most C-fiber nociceptors are polymodal (i.e., respond to multiple noxious stimulus modalities, such as mechanical and thermal); nevertheless, these stimuli are perceived as distinct. Therefore, it is believed that discrimination among these modalities only occurs at spinal or supraspinal levels of processing. Here, we provide evidence to the contrary. Genetic ablation in adulthood of unmyelinated sensory neurons expressing the G protein-coupled receptor Mrgprd reduces behavioral sensitivity to noxious mechanical stimuli but not to heat or cold stimuli. Conversely, pharmacological ablation of the central branches of TRPV1+ nociceptors, which constitute a nonoverlapping population, selectively abolishes noxious heat pain sensitivity. Combined elimination of both populations yielded an additive phenotype with no additional behavioral deficits, ruling out a redundant contribution of these populations to heat and mechanical pain sensitivity. This double-dissociation suggests that the brain can distinguish different noxious stimulus modalities from the earliest stages of sensory processing.
Testing the Feasibility and Usability of a Novel Smartphone-Based Self-Management Support System for Dialysis Patients: A Pilot Study

Background Diet and fluid restrictions that need continuous self-management are among the most difficult aspects of dialysis treatment. Smartphone applications may be useful for supporting self-management. Objective Our objective is to investigate the feasibility and usability of a novel smartphone-based self-management support system for dialysis patients. Methods We developed the Self-Management and Recording System for Dialysis (SMART-D), which supports self-monitoring of three mortality-related factors that can be modified by lifestyle: interdialytic weight gain and predialysis serum potassium and phosphorus concentrations. Data is displayed graphically, with all data evaluated automatically to determine whether they achieve the values suggested by the Japanese Society for Dialysis Therapy guidelines. In a pilot study, 9 dialysis patients used SMART-D system for 2 weeks. A total of 7 of them completed questionnaires rating their assessment of SMART-D’s usability and their satisfaction with the system. In addition, the Kidney Disease Quality of Life scale was compared before and after the study period. Results All 9 participants were able to use SMART-D with no major problems. Completion rates for body weight, pre- and postdialysis weight, and serum potassium and phosphorus concentrations were, respectively, 89% (SD 23), 95% (SD 7), and 78% (SD 44). Of the 7 participants who completed the usability survey, all were motivated by the sense of security derived from using the system, and 6 of the 7 (86%) reported that using SMART-D helped improve their lifestyle and self-management. Conclusions Using SMART-D was feasible, and the system was well regarded by patients. Further study with larger scale cohorts and longer study and follow-up periods is needed to evaluate the effects of SMART-D on clinical outcomes and quality of life.
Insulin Resistance and Hypertension in Obese Youth With Sleep-Disordered Breathing Treated With Positive Airway Pressure: A Prospective Multicenter Study.

STUDY OBJECTIVES There is evidence that cardiometabolic disease associated with obesity and sleep-disordered breathing (SDB) in adults is present in youth. SDB is often treated with positive airway pressure (PAP) in youth with obesity. Our aims were to determine: (1) the prevalence of cardiometabolic disease and (2) whether PAP improves markers of cardiometabolic disease, in youth with obesity and newly diagnosed moderate-severe SDB. METHODS A prospective multicenter cohort study was conducted in youth (8 to 16 years old) with obesity, prescribed PAP therapy for newly diagnosed moderate-severe SDB. Assessments occurred at baseline and at 6 and 12 months. Outcomes included markers of insulin resistance (change in homeostasis model assessment of insulin resistance (HOMA-IR) at 6 months = primary outcome), hypertension (24-hour ambulatory/blood pressure) and inflammation (high-sensitivity C-reactive protein: hs-CRP). RESULTS Twenty-seven participants were enrolled. Of those with baseline testing available, 10/25 (40%) had HOMA-IR above the 97th percentile, 10/23 (44%) were hypertensive, 16/23 (70%) had loss of nocturnal blood pressure dip and hs-CRP was elevated in 16/27 (64%). There were no significant changes over time in markers of metabolic dysfunction or blood pressure, nor between PAP-adherent and non-adherent subgroups. CONCLUSIONS In youth with obesity and SDB, metabolic dysfunction and hypertension were highly prevalent. There were no statistically significant improvements in cardiometabolic markers 1 year after the prescription of PAP therapy, although clinically relevant improvements were seen in insulin resistance and systolic blood pressure load, important predictors of future risk of cardiovascular disease. Larger, longer-term studies are needed to determine whether PAP improves cardiometabolic outcomes in obese youth. COMMENTARY A commentary on this article appears in this issue on page 1025.
Medical Nutrition Therapy for Patients With Advanced Systemic Sclerosis (MNT PASS): A Pilot Intervention Study

Background: The objective of this study was to demonstrate the feasibility and associations with short-term outcomes of a medical nutrition therapy (MNT) intervention in patients with systemic scleroderma (SSc). Materials and Methods: Eighteen patients with SSc, gastrointestinal (GI) involvement, and unintentional weight loss were consented and recruited for a 6-week MNT intervention, in addition to their usual medical management. MNT emphasized increased calorie and protein intake, modified textures, and lifestyle modifications. Symptoms, anthropometrics, diet (24-hour recall), and body composition (dual-energy x-ray absorptiometry) were assessed pre- and postintervention. Sarcopenia was defined as appendicular lean height (ALH) for women <5.45 kg/m2 and for men <7.26 kg/m2. Descriptive, parametric, and nonparametric statistics were conducted. Results: Participants (n = 18) were predominantly white (78%), female (89%), malnourished (83%), and 51.3 ± 11.0 years of age with a body mass index of 22.6 ± 6.7 kg/m2. Significant decreases in nutrition symptom scores (12.8 vs 7.6, P < .05) and improvements in ALH (5.6 ± 0.8 vs 5.8 ± 0.8 kg/m2, respectively; P = .05) occurred pre- vs postintervention, respectively (n = 14). Sarcopenia was observed in 54% of participants at baseline and 39% at follow-up (P = .02). Caloric intake (1400 vs 1577 kcal/d, P = .12) and macronutrient distribution (ie, % fat, protein, carbohydrate) did not change significantly pre- vs postintervention, respectively. Conclusions: Individually tailored MNT can improve symptom burden and potentially ALH in patients with SSc involving the GI tract. This study underscores the clinical potential of multidisciplinary patient management and the need for larger nutrition intervention trials of longer duration in these patients.
Moving forward with treatment options for HIV-infected children

ABSTRACT Introduction: Current international guidelines recommend to treat all HIV-1 infected patients regardless of CD4 cell count. Despite the remarkable worldwide progress for universal access to antiretroviral during the last decade, the pediatric population remains fragile due to lack of randomized studies, inappropriate antiretroviral formulations, adherence difficulties, drug toxicity and development of resistance. Areas covered: This review summarizes the latest recommendations and advances for the treatment of HIV-infected children and highlights the potential complications of a lifelong antiretroviral treatment initiated early in life. Expert opinion: International guidelines recommend to start combination antiretroviral therapy (cART) as fast as possible in all children diagnosed with HIV-1. The principal goal is to improve survival and reduce mortality as well as rapidly decrease HIV reservoirs. This remains a challenge in resource-limited settings were diagnostic tools and treatment access may be limited. Different new strategies are in the pipeline such as immunotherapy in combination with very early cART initiation to seek remission or functional cure. For the time being and awaiting for long term remission or cure, there is a need for further pharmacokinetics studies, more pediatric formulations with improved palatability and implementation of randomized trials for the newer antiretroviral drugs.
The role of molecular breast imaging in predicting complete tumor response to treatment and residual tumor extent following neoadjuvant therapy

The aim of the present study was to investigate the usefulness of molecular breast imaging (MBI) in predicting complete tumor response to treatment and residual tumor extent following neoadjuvant therapy. A consecutive series of 43 female patients with large or locally advanced primary breast cancer, scheduled for surgery following neoadjuvant therapy, was retrospectively reviewed. Prior to surgery, all patients underwent MBI using a high-resolution semiconductor-based device for image acquisition. MBI data were correlated with surgical histopathological findings. Spearman's correlation coefficient was calculated to assess differences in residual tumor size with MBI and histopathological examination. From the images obtained using MBI, 7 patients were negative for residual tumors with pathological complete response (specificity, 100%) and positive in 34/36 patients with residual disease (sensitivity, 94.4%), including 26/27 patients with unifocal and 8/9 patients with multicentric/multifocal tumors, 5 of which exhibited multiple microscopic foci scattered in a fibrotic area. Overall accuracy was 95.3% and the positive predictive value (PPV) and negative predictive value (NPV) were 100 and 77.8%, respectively. MBI was false-negative in one patient with a 2.5-cm invasive ductal carcinoma located close to the chest wall and in one patient with microscopic foci of epithelial carcinoma. In the patients with unifocal residual tumors, correlation of tumor size between MBI and histopathology was r=0.981 (P<0.0001); however, MBI overestimated the number of lesions in one of these cases. In the patients with multifocal/multicentric tumors, MBI adequately assessed residual tumor extent in 5/8 positive cases, overestimating the number of lesions in one case and underestimating tumor extent in 2 further cases with microscopic foci scattered in a fibrotic area. MBI proved to be a highly accurate diagnostic tool in predicting complete tumor response to neoadjuvant therapy and residual tumor extent, correlating with surgical histopathological findings in 86% of overall cases. A positive result was always associated with the presence of residual disease and MBI tumor size was strongly correlated with histopathological analysis mainly in unifocal residual tumors.
Down-Regulation of TGF-β Expression Sensitizes the Resistance of Hepatocellular Carcinoma Cells to Sorafenib

Purpose Sorafenib, a multikinase inhibitor, is the standard therapy for patients with advanced-stage hepatocellular carcinoma (HCC). However, resistance develops to the treatment, therefore, we tried to unravel the underlying mechanism in the resistance of HCC cells to sorafenib via the development of more effective therapeutic strategies. Materials and Methods Various liver cancer cell lines were treated with either sorafenib only or with sorafenib after infection of adenovirus expressing short hairpin RNA (shRNA) against transforming growth factor-β (TGF-β) and p38 activity was examined using western blotting. Results p38 MAP kinase activity was inhibited by low concentrations of sorafenib, which could potentially lead to sorafenib resistance in HCC cell lines. Subsequently, we used constitutive form of MKK3/6 (MKK3/6E) to confirm that massive cell death was induced by the activation of p38, and demonstrated the ability to activate p38 without any stimulation. In addition, sorafenib resistance was reduced by the activation of p38. Subsequently, we confirmed that TGF-β shRNA effectively recovered the phosphorylation of p38 inhibited by sorafenib, and increased the sensitivity of HCC cells to sorafenib, thereby inducing cell death and overcoming the resistance of HCC cells to sorafenib. Conclusion Our study provides a new therapeutic strategy for HCC that overcomes the resistance of HCC to sorafenib by down-regulation of TGF-β.
Biotechnological conversion of methane to methanol: evaluation of progress and potential

Sources of methane are numerous, and vary greatly in their use and sustainable credentials. A Jekyll and Hyde character, it is a valuable energy source present as geological deposits of natural gas, however it is also potent greenhouse gas, released during many waste management processes. Gas-to-liquid technologies are being investigated as a means to exploit and monetise non-traditional and unutilised methane sources. The product identified as having the greatest potential is methanol due to it being a robust, commercially mature conversion process from methane and its beneficial fuel characteristics. Commercial methane to methanol conversion requires high temperatures and pressures, in an energy intensive and costly process. In contrast methanotrophic bacteria perform the desired transformation under ambient conditions, using methane monooxygenase (MMO) enzymes. Despite the great potential of these bacteria a number of biotechnical difficulties are hindering progress towards an industrially suitable process. We have identified five major challenges that exist as barriers to a viable conversion process that, to our knowledge, have not previously been examined as distinct process challenges. Although biotechnological applications of methanotrophic bacteria have been reviewed in part, no review has comprehensively covered progress and challenges for a methane to methanol process from an industrial perspective. All published examples to date of methanotroph catalysed conversion of methane to methanol are collated, and standardised to allow direct comparison. The focus will be on conversion of methane to methanol by whole-cell, wild type, methanotroph cultures, and the potential for their application in an industrially relevant process. A recent shift in the research community focus from a mainly biological angle to an overall engineering approach, offers potential to exploit methanotrophs in an industrially relevant biotechnological gas-to-liquid process. Current innovations and future opportunities are discussed.
Deregulation of MicroRNAs in Gastric Lymphomagenesis Induced in the d3Tx Mouse Model of Helicobacter pylori Infection

Helicobacter pylori infection is considered as an excellent model of chronic inflammation-induced tumor development. Our project focuses on gastric MALT lymphoma (GML) related to H. pylori infection and mediated by the chronic inflammatory process initiated by the infection. Recently, microRNAs (miRNAs) have emerged as a new class of gene regulators, which play key roles in inflammation and carcinogenesis acting as oncogenes or tumor suppressors. Their precise characterization in the development of inflammation and their contribution in regulating host cells responses to infection by H. pylori have been little explored. Our goal was to analyze the changes in miRNAs in a GML mouse model using BALB/c mice thymectomized at day 3 post-birth (d3Tx model) and to clarify their implication in GML pathogenesis. PCR array followed by RT-qPCR identified five miRNAs (miR-21a, miR-135b, miR-142a, miR-150, miR-155) overexpressed in the stomachs of GML-developing d3Tx mice infected by H. pylori. The analysis of their putative targets allowed us to identify TP53INP1, an anti-proliferative and pro-apoptotic protein, as a common target of 4 of the 5 up-regulated miRNAs. We postulate that these miRNAs may act in synergy to promote the development of GML. miR-142a was also overexpressed in mouse sera samples and therefore could serve as a diagnostic marker. In situ hybridization on gastric samples with miR-142a revealed a global up-regulation of this miRNA by the tumor microenvironment at the lymphoma stage. Dysregulation of miR-21a, miR-135b, miR-142a, miR-150, miR-155 could play a critical role in the pathogenesis of GML and might offer potential applications as therapeutic targets and novel biomarkers for this disease.
Decompressive craniectomy bone flap hinged on the temporalis muscle: A new inexpensive use for an old neurosurgical technique

Background: The neurosurgical procedure of hinge decompressive craniectomy (hDC), or hinge craniotomy (HC), as described from units in the advanced countries makes use of metallic implants, usually titanium plates and screws, which may not be economically viable in resource-limited practice settings. Methods: We describe our surgical techniques for performing this same procedure of hDC in a developing country using the patient's own temporalis muscle instead of any other potentially costly implants. Results: The technique as described appears to be successful in achieving intracranial decompression in cases of traumatic brain swelling in which it has been used. Clinical and radiological illustrations of the feasibility, and practical utility, of the procedures in four clinical scenarios of traumatic brain injury are presented. Like all other techniques of HC, this new surgical technique of hDC temporalis saves the survivors the added imperative of future cranioplasty of the usual postcraniectomy skull defect. Unlike the others, the procedure eliminates the added cost of the metallic implants needed to perform the former techniques. Conclusions: The procedure of hDC temporalis appears to be a viable option for performing the surgical procedure of HC and has added cost-cutting economic benefits for resource-limited practice settings.
Joint Power and Antenna Selection Optimization in Large Cloud Radio Access Networks

Large multiple-input multiple-output (MIMO) networks promise high energy efficiency, i.e., much less power is required to achieve the same capacity compared to the conventional MIMO networks if perfect channel state information (CSI) is available at the transmitter. However, in such networks, huge overhead is required to obtain full CSI especially for Frequency-Division Duplex (FDD) systems. To reduce overhead, we propose a downlink antenna selection scheme, which selects S antennas from M > S transmit antennas based on the large scale fading to serve K ≤ S users in large distributed MIMO networks employing regularized zero-forcing (RZF) precoding. In particular, we study the joint optimization of antenna selection, regularization factor, and power allocation to maximize the average weighted sum-rate. This is a mixed combinatorial and non-convex problem whose objective and constraints have no closed-form expressions. We apply random matrix theory to derive asymptotically accurate expressions for the objective and constraints. As such, the joint optimization problem is decomposed into subproblems, each of which is solved by an efficient algorithm. In addition, we derive structural solutions for some special cases and show that the capacity of very large distributed MIMO networks scales as O(KlogM) when M→∞ with K, S fixed. Simulations show that the proposed scheme achieves significant performance gain over various baselines.
Comparative Studies of Ni, Cd, Mn, Co, Pb, Cr and Zn in Hair, Nail and Plasma of Smokers and Non-smokers Subjects of Sargodha Zone

The present research work was focused to quantify and compare the level of most commonly exposed heavy metals in smokers and non-smokers subjects of different zones of Sargodha region. Heavy metals are generally considered and have been reported, play a very crucial role in destabilizing the immune system and producing carcinogenity. In this study we assessed and compared the level of Ni, Cd, Mn, Co, Pb, Cr and Zn in hair, nail and plasma samples of similar age group smokers and nonsmokers. About 42 smoker and 42 non-smoker subjects were selected form Sargodha region, from which 21 were male and 21 female. Levels of the heavy metals were compared on different parameters including sex and age. Analysis was performed using Atomic Absorption Spectrophotometer (AAS). Total mean value of Zn was lower in smokers than non-smokers, whereas elevation of Cd, Mn, Co, Pb, Mn and Ni was observed in smokers as compared to non-smokers. Male smokers showed significantly (p 45 years. However, lower concentration of Zn and Co was observed smokers of age > 45 years. The result showed significant impact of heavy metal accumulation via smoking on initiation of different fatal diseases in human beings. In conclusion such fatal diseases coulod be overcome by reducing exposure to heavy metals.