Miracle-dz/UniFAR-FTUs huggingface dataset:
Tuberculosis Vaccine Development: Progress in Clinical Evaluation

Tuberculosis (TB) is the leading killer among all infectious diseases worldwide despite extensive use of the Mycobacterium bovis bacille Calmette-Guérin (BCG) vaccine. A safer and more effective vaccine than BCG is urgently required. More than a dozen TB vaccine candidates are under active evaluation in clinical trials aimed to prevent infection, disease, and recurrence. SUMMARY Tuberculosis (TB) is the leading killer among all infectious diseases worldwide despite extensive use of the Mycobacterium bovis bacille Calmette-Guérin (BCG) vaccine. A safer and more effective vaccine than BCG is urgently required. More than a dozen TB vaccine candidates are under active evaluation in clinical trials aimed to prevent infection, disease, and recurrence. After decades of extensive research, renewed promise of an effective vaccine against this ancient airborne disease has recently emerged. In two innovative phase 2b vaccine clinical trials, one for the prevention of Mycobacterium tuberculosis infection in healthy adolescents and another for the prevention of TB disease in M. tuberculosis-infected adults, efficacy signals were observed. These breakthroughs, based on the greatly expanded knowledge of the M. tuberculosis infection spectrum, immunology of TB, and vaccine platforms, have reinvigorated the TB vaccine field. Here, we review our current understanding of natural immunity to TB, limitations in BCG immunity that are guiding vaccinologists to design novel TB vaccine candidates and concepts, and the desired attributes of a modern TB vaccine. We provide an overview of the progress of TB vaccine candidates in clinical evaluation, perspectives on the challenges faced by current vaccine concepts, and potential avenues to build on recent successes and accelerate the TB vaccine research-and-development trajectory.
Patent foramen ovale: Connecting dots from massive pulmonary embolism to acute ischemic stroke

© 2019 Indian Chest Society | Published by Wolters Kluwer Medknow This is an open access journal, and articles are distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as appropriate credit is given and the new creations are licensed under the identical terms. Access this article online Quick Response Code: Website:
A narrative review of adjuvants in in vitro fertilisation: evidence for good clinical practice

Abstract A review of studies published between January 1, 1984 and January 31, 2019 was performed with the aim of analysing the efficacy and adverse effects of commonly used adjuvants to in vitro fertilisation. The authors preferentially selected recent systematic reviews and randomised control trials (where available) from an electronic literature search. The review showed that low molecular weight heparin, corticosteroids and embryo glue may be of use in selected patient groups. Other adjuncts (such as growth hormone, assisted hatching, endometrial disruption and dehydroepiandrosterone) cannot currently be recommended as collated results showed no overall benefit to clinical pregnancy rates or live birth rates. There is a significant lack of robust evidence in this field, and areas in particular need of further research have been highlighted. In conclusion, caution should be exercised in prescribing adjuvants in in vitro fertilisation, either individually or in combination as further research is needed to ascertain their efficacy. Many adjuvants carry the risk of adverse effects which should also be considered. Patients should be clearly informed of the evidence, and where it is lacking, for these treatments. There is a need for further good quality trials to address the questions regarding best practice.
Artificial Intelligence in Lung Cancer Pathology Image Analysis

Objective: Accurate diagnosis and prognosis are essential in lung cancer treatment selection and planning. With the rapid advance of medical imaging technology, whole slide imaging (WSI) in pathology is becoming a routine clinical procedure. An interplay of needs and challenges exists for computer-aided diagnosis based on accurate and efficient analysis of pathology images. Recently, artificial intelligence, especially deep learning, has shown great potential in pathology image analysis tasks such as tumor region identification, prognosis prediction, tumor microenvironment characterization, and metastasis detection. Materials and Methods: In this review, we aim to provide an overview of current and potential applications for AI methods in pathology image analysis, with an emphasis on lung cancer. Results: We outlined the current challenges and opportunities in lung cancer pathology image analysis, discussed the recent deep learning developments that could potentially impact digital pathology in lung cancer, and summarized the existing applications of deep learning algorithms in lung cancer diagnosis and prognosis. Discussion and Conclusion: With the advance of technology, digital pathology could have great potential impacts in lung cancer patient care. We point out some promising future directions for lung cancer pathology image analysis, including multi-task learning, transfer learning, and model interpretation.
Same-Day Patient Consultation and Cochlear Implantation: Innovations in Patient-Centered Health Care Delivery.

OBJECTIVE To develop and implement a streamlined, patient-centered service delivery model for patients referred for cochlear implantation (CI) at a high-volume academic center. PATIENTS CI candidate adults. INTERVENTIONS CI, implementation of new CI delivery model. MAIN OUTCOME MEASURES Referral-to-surgery time, patient travel burden. RESULTS Data from 206 adults that underwent CI were used to develop a process map of the initial operational state from referral date to day of surgery (referral-to-surgery time). The initial referral-to-surgery time was 136 days on average, yet the average total work time by all involved providers was 17.6 hours. Prolonged wait times were associated with the following preoperative tasks: appointment scheduling, insurance approval, device ordering and shipment, and surgical scheduling. Patients traveled to the institution on at least two occasions for appointments. A new bundled, patient-centered CI delivery model was developed to address prolonged wait times, travel burden, and process inefficiencies. The new model implemented an interactive electronic medical record, coordinated appointments with same-day surgery, and stocked device inventory to reduce the referral-to-surgery time to 24 days-an improvement of 112 days. In the new model, new patient consultation and surgery were completed in one day, reducing the patient travel burden to the institution. CONCLUSIONS The new CI program demonstrates that delivery innovations can have a substantial impact on measures of patient convenience and experience, and that these results are achievable without new technologies or changes in medical management. With a focus on patient-centered design, health care delivery models can be augmented to increase value for patients.
Increased rate of FEV1 decline in HIV patients despite effective treatment with HAART

Introduction Previous studies have reported that the rate of FEV1 decline over time is increased in HIV patients but the mechanisms underlying this observation are unclear. Since current HIV treatment with Highly Active Antiretroviral Therapy (HAART) results in very good immune-viral control, we hypothesized that HAART should normalize the elevated rate of FEV1 decline previously reported in HIV patients if it was somehow related to the immune alterations caused by HIV, particularly in never smokers or quitters, since smoking is a well established risk factor for accelerated FEV1 decline in the general population. Methods We explored this hypothesis in a prospectively recruited cohort of 188 HIV (smoker and non-smoker) patients treated with HAART in Palma de Mallorca (Spain) and followed-up for 6 years. The cross-sectional characteristics of this cohort have been published elsewhere. Results We found that: (1) HAART resulted in good immune-viral control; (2) the rate of FEV1 decline remained abnormally elevated, even in non-smokers and quitters; and, (3) alcohol abuse during follow-up was related to FEV1 decline in these patients. Discussion Despite adequate immune-viral control by HAART, lung function decline remains increased in most HIV patients, even in non-smokers and quitters. Alcohol abuse is a preventable risk factor to decrease the accelerated FEV1 decline in this population.
Necesidades sociales de los enfermos esquizofrénicos en Navarra

The increase in the need for aid constitutes a priority problem of social policy in the developed countries. The need for aid is framed within the intersection of social and health services, and requires a new conception of the problems and new models of intervention. In 1986, with the Mental Health Plan of Navarra, a new form of care was put forward, centred on care in the community. At present, important differences can be appreciated, such as the insufficiency of alternative health and social programs in the community, as well as the difficulty of co-ordinating them. Facing this situation, the social workers of the Mental Health Network carried out a study that evaluated the social needs of the patients who were attended to by the Mental Health Network, with attention paid to socio-demographic aspects, the clinic and the type of social resources that they needed. Following this study, and on the basis of the discussion that it gave rise to, new forms of intervention have been proposed in the care of the mentally ill, developing the concept of socio-health care.
The role of Ames dwarfism and calorie restriction on gut microbiota.

The gut microbiome (GM) represents a large and very complex ecosystem of different microorganisms. There is an extensive interest in the potential role of the GM in different diseases including cancer, diabetes, cardiovascular diseases, and aging. The GM changes over the lifespan and is strongly associated with various age-related diseases. Ames dwarf (df/df) mice are characterized by an extended life- and healthspan, and although these mice are protected from many age-related diseases, their microbiome has not been studied. To determine the role of microbiota on longevity animal models, we investigated the changes in the GM of df/df and Normal control (N) mice, by comparing parents before mating and littermate mice at three distinct time points during early life. Furthermore, we studied the effects of a 6-month calorie restriction (CR), the most powerful intervention extending the lifespan. Our data revealed significant changes of the GM composition during early life development, and we detected differences in the abundance of some bacteria between df/df and N mice, already in early life. Overall, the variability of the microbiota by genotype, time-point and breeding pair showed significant differences. In addition, CR caused significant changes in microbiome according to gastrointestinal (GI) location (distal colon, ileum and cecum), genotype and diet. However, the overall impact of the genotype was more prominent than that of the CR. In conclusion, our findings suggest that the gut microbiota plays an important role during post-natal development in long-living df/df mice and CR dietary regimen can significantly modulate the GM.
Surgery as a Viable Alternative First-Line Treatment for Prolactinoma Patients. A Systematic Review and Meta-Analysis

Abstract Context The improved remission and complication rates of current transsphenoidal surgery warrant reappraisal of the position of surgery as a viable alternative to dopamine agonists in the treatment algorithm of prolactinomas. Objective To compare clinical outcomes after dopamine agonist withdrawal and transsphenoidal surgery in prolactinoma patients. Methods Eight databases were searched up to July 13, 2018. Primary outcome was disease remission after drug withdrawal or surgery. Secondary outcomes were biochemical control and side effects during dopamine agonist treatment and postoperative complications. Fixed- or random-effects meta-analysis was performed to estimate pooled proportions. Robustness of results was assessed by sensitivity analyses. Results A total of 1469 articles were screened: 55 (10 low risk of bias) on medical treatment (n = 3564 patients) and 25 (12 low risk of bias) on transsphenoidal surgery (n = 1836 patients). Long-term disease remission after dopamine agonist withdrawal was 34% (95% confidence interval [CI], 26-46) and 67% (95% CI, 60-74) after surgery. Subgroup analysis of microprolactinomas showed 36% (95% CI, 21-52) disease remission after dopamine agonist withdrawal, and 83% (95% CI, 76-90) after surgery. Biochemical control was achieved in 81% (95% CI, 75-87) of patients during dopamine agonists with side effects in 26% (95% CI, 13-41). Transsphenoidal surgery resulted in 0% mortality, 2% (95% CI, 0-5) permanent diabetes insipidus, and 3% (95% CI, 2-5) cerebrospinal fluid leakage. Multiple sensitivity analyses yielded similar results. Conclusions In the majority of prolactinoma patients, disease remission can be achieved through surgery, with low risks of long-term surgical complications, and disease remission is less often achieved with dopamine agonists.
Whole lung lavage using a rapid infusion system to treat a patient with pulmonary alveolar proteinosis

Whole lung lavage (WLL) is a therapeutic procedure to remove accumulated material by infusing and draining the lungs with lavage fluid. This procedure has been regarded as the current standard of care to treat pulmonary alveolar proteinosis. However, the WLL protocol has not yet been standardized and the technique has been refined and modified a number of times. A rapid infusion system is a device used to infuse blood or other fluids at precise rates and normothermic conditions. This device is not typically used in WLL, which relies on the passive infusion of fluids using the gravitational force. However, in this study we performed WLL using a rapid infusion system, since we aimed to take advantage of its shorter operation time and greater degree of control over fluid volume and temperature. The patient’s symptoms improved without the occurrence of any complications.
Theoretical Investigation of Wideband Longitudinally Coupled Resonator Filter Using Lithium Niobate Thin Plates

This paper describes the possibility of wideband longitudinally coupled resonator filters (LCRFs) composed of LN-based thickness-shear BAW resonators (TSBARs). Not so small acoustic impedance is required for the coupling layer between stacked resonators because of extremely large electromechanical coupling factor $k^{2}$ of the structure. As the coupler, $\text{SiO}_{2}$ and $\mathbf{SiOC}$ with different C content are applied, and achievable performances are compared. When $\mathbf{SiO_{2}}$ is employed, although its acoustic impedance is slightly larger than optimal, flat and wide passband can be also achievable giving small inductors in series. It is also shown that flat and very wide passband can be realizable when SiOC with proper C content is used as the coupler.
Cuscutae Japonicae Semen Ameliorates Memory Dysfunction by Rescuing Synaptic Damage in Alzheimer’s Disease Models

Alzheimer’s disease (AD) is the most common type of dementia in the elderly. It is characterized by the accumulation of amyloid-beta (Aβ) and progressive cognitive impairment. To alleviate the symptoms of AD, functional foods and nutrients have been used for centuries. In this study, we investigated whether Cuscutae Japonicae Semen (CJS), a medicinal food traditionally used in East Asia, has effects on memory improvement and synapse protection in AD. We orally administered CJS to 5x familiar AD (5xFAD) transgenic mice and performed the Morris water maze test. The results showed that CJS treatment ameliorated the decline of memory function. Then, we demonstrated that CJS attenuated the degeneration of pre- and post-synaptic proteins in the hippocampi of 5xFAD mice. To demonstrate the effects of CJS in vitro, we treated Aβ in primary neuronal culture with CJS and observed that CJS rescued the loss of functional synapses. The protective effects of CJS on the synapse were due to the inhibition of activated caspase-3 expression. Additionally, CJS inhibited the phosphorylation of glycogen synthase kinase-3β and tau proteins, which contribute to synaptic dysfunction. Taken together, our results suggest that CJS is efficient in alleviating memory loss by rescuing caspase-3-mediated synaptic damage in AD treatment.
Pulmonary T-cell lymphoma masquerading as eosinophilic pneumonitis

Primary pulmonary T-cell lymphoma is an unusual subtype of peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS). This is a general term used to describe a diverse group of T-cell-type lymphomas that would otherwise not be classified as a PTCL. Among non-Hodgkin's lymphomas, PTCL accounts for 12% of cases. PTCL-NOS accounts for approximately 25% of all PTCL cases. Primary pulmonary T-cell lymphoma is associated with unfavorable outcomes and has a poor prognosis. Being a rare disease, epidemiological data regarding primary pulmonary T-cell lymphoma continues to be sparse at this time. We present a case of PTCL, which was misdiagnosed as eosinophilic pneumonitis (EP) based on samples obtained from transbronchial cryobiopsy. To our knowledge, this is the first reported case of PTCL masquerading as EP.
Vitamin D in chronic obstructive pulmonary disease and asthma in Indian population

Rajaram et al. in their hospital-based study among 18–50-year-old South Indian patients with bronchial asthma demonstrated the effects of genetic polymorphisms in Vitamin D metabolic pathway on Vitamin D level and asthma control. [5] They concluded that Vitamin D receptor polymorphism (rs2228570) was found to be protective against asthma exacerbations. There were poor correlations and insignificant associations of single-nucleotide polymorphisms and serum 25-hydroxyvitamin D levels among asthma patients and healthy controls. The Global Initiative for Asthma guidelines do not support the supplementation of Vitamin D for the prevention of exacerbation of asthma. [11] A systematic review and meta-analysis of individual participant data from seven randomized controlled trials by Jolliffe et al. studied the pooled estimate of the protective effects of Vitamin D against asthma exacerbations requiring treatment with systemic corticosteroids. [12] It also investigated the effect of Vitamin D supplementation on risk of asthma exacerbation according to baseline 25-hydroxyvitamin D concentrations. All these seven randomized controlled trials were conducted at secondary and tertiary care levels, among children and adults. The Vitamin D supplementation dosage and schedule varied among the studies. All the studies gave oral Vitamin D3 supplementation to participants in the intervention arm. Minimum dose given was 500 IU/day to a maximum of 4000 IU/day. Three of the randomized controlled trials also gave a bolus dose of Vitamin D3 ranging from 100000 IU to 120000 IU. [13-15] The authors concluded that Vitamin D supplementation reduced asthma exacerbations treated with oral corticosteroids when compared with placebo. Nevertheless, differences across subgroups, including baseline 25-hydroxyvitamin D status, did not reach statistical significance. Therefore, which group of patients will have preventive effects of Vitamin D supplementation is still not known.
Age at first HIV test for MSM at a community health clinic in Los Angeles

ABSTRACT Young MSM, especially ethnic and racial minority young MSM, bear a disproportionate burden of new HIV infections. This group also has the highest rates of undiagnosed infection and lowest rates of viral suppression. Previous research indicates that young MSM are testing for HIV too late, which may explain why rates of new HIV infection are rising in young Hispanic MSM and not falling in young Black and White MSM despite advances in preventive medications. Analysis of our sample showed an overall average age at first HIV test of approximately 26. The average age at first HIV test was 25.5 years for Black/African American individuals, 24.7 years for Hispanic individuals, and 28 years for White individuals. More testing resources and innovative outreach methods are needed to increase rates of testing among young MSM.
Prognostic impact of local radiotherapy on metastatic urothelial carcinoma patients receiving systemic chemotherapy.

OBJECTIVE To clarify the prognostic impact of local radiotherapy on metastatic urothelial carcinoma patients treated by systemic chemotherapy. METHODS Of the 228 metastatic urothelial carcinoma patients treated with systemic chemotherapy, 97 received radiotherapy mainly to metastatic sites. In patients for whom the purpose of radiotherapy was not specified, more than 50 Gy irradiation was considered to be for disease consolidation for survival analysis, while less than 50 Gy was categorized as palliation. According to the Kaplan-Meier method, we analysed overall survival from the initiation of treatment for metastatic urothelial carcinoma until death or the last follow-up, using the log-rank test to assess the significance of differences. The Cox model was applied for prognostic factor analysis. RESULTS Overall, there was no significant difference in survival between patients with and those without radiotherapy (P = 0.1532). When analysing the patients undergoing consolidative radiotherapy separately, these 25 patients showed significantly longer survival than the 72 patients with palliative radiotherapy (P = 0.0047), with a 3-year overall survival of 43.3%. Of the present cohort, 22 underwent metastasectomy for disease consolidation, and there was no overlapping case between the metastasectomy cohort and cohort receiving consolidative radiotherapy. After controlling for four independent prognostic factors (sex, performance status, haemoglobin level and number of organs with metastasis) in our previous study, radiotherapy for disease consolidation showed a marginal value (hazard ratio = 0.666, P = 0.0966), while metastasectomy remained significant (hazard ratio = 0.358, P = 0.0006). CONCLUSIONS In the selected patients, long-term disease control could be achieved after consolidative radiotherapy for metastatic urothelial carcinoma disease. Our observations suggest that local ablative therapy (surgery or radiotherapy) could facilitate long-term disease control. However, the treatment decision should be individualized because of the lack of randomized control trials.
Current advances in research in treatment and recovery: Nicotine addiction

This review covers the changing tobacco product marketplace and evidence-based approaches to prevent and treat nicotine addiction. The health harms of combusted tobacco use are undeniable. With market and regulatory pressures to reduce the harms of nicotine delivery by combustion, the tobacco product landscape has diversified to include smokeless, heated, and electronic nicotine vaping products. Products of tobacco combustion are the main cause of smoking-induced disease, and nicotine addiction sustains tobacco use. An understanding of the biology and clinical features of nicotine addiction and the conditioning of behavior that occurs via stimuli paired with frequent nicotine dosing, as with a smoked cigarette, is important for informing pharmacologic and behavioral treatment targets. We review current advances in research on nicotine addiction treatment and recovery, with a focus on conventional combustible cigarette use. Our review covers evidence-based methods to treat smoking in adults and policy approaches to prevent nicotine product initiation in youth. In closing, we discuss emerging areas of evidence and consider new directions for advancing the field.