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Background: Telemedicine-assisted buprenorphine (BNX) induction (TABI) has the potential to reduce the treatment gap for opioid use disorder. Aim: This study investigated the acceptability and feasibility of TABI in India. This was a retrospective study from a specialized addiction treatment center in a teaching hospital. Methods: TABI was introduced in November 2022; patients enrolled till May 2023 were included in the analysis. Feasibility was assessed by the proportion of patients who completed the TABI program, continued treatment for at least 3 months, and self-reported nonprescription opioid use during and after TABI. Acceptability was measured by patient satisfaction with TABI. Results: Sixty patients were enrolled: Fifty-three patients (88.3%) were retained during the TABI program, and 50 patients (83.3%) remained in treatment at the 3-month follow-up. Thirty-five patients (58.3%) reported using nonprescription opioids during TABI, and 28 patients (46.7%) reported such use after completing the program. Thirty-five (58.3%) were satisfied with the program, and 15 (25%) said they would recommend it to others. Patients who missed scheduled in-person appointments (P < .001) at 1 week, did not return unused BNX-naloxone (P < .001), and were not satisfied (P = .004) were more likely to report nonprescription opioid use. Those who attended the in-person follow-up at 1 week (P = .004) and were satisfied (P = .01) and did not use nonprescription opioids either during (P = .003) or after (P < .001) TABI were more likely to be retained in treatment at 3 months. Conclusion: The study shows TABI’s acceptability and feasibility in a specialized addiction treatment setting; further research is needed for broader applicability.

Background: Pregabalin, approved for various medical conditions, has shown increasing misuse potential globally. However, limited research exists on pregabalin dependence in India. This study aimed to investigate the prevalence and characteristics of pregabalin dependence among individuals seeking substance use disorder (SUD) treatment in North India. Methods: A cross-sectional, analytical study was conducted on patients enrolled between August 2022 and July 2023 at an academic institution-based addiction treatment center. Case records of patients with pregabalin dependence were retrieved and compared with controls with opioid dependence but no history of pregabalin use. Results: Among 3766 registered patients, 135 had pregabalin dependence (prevalence: 3.58 per 100 registered patients). Pregabalin-dependent patients were male, with a median usage duration of eight months and a median daily dose of 1200 mg. Most had concurrent opioid dependence, primarily heroin, used via the injection route. The odds of pregabalin dependence among those with opioid dependence were significantly higher than those with other substance dependence (OR 1.44, 95% CI 1.13–1.85). Reasons for pregabalin use included opioid craving reduction, sedation, and euphoria. Patients with pregabalin dependence were more likely to have lower socioeconomic status (P < 0.0001) and urban residence (P = 0.032), an earlier age of substance use initiation (P = 0.02) and treatment seeking (P < 0.0001), and a higher co-occurrence of psychiatric disorders (P = 0.007) and less occurrence of alcohol dependence (P = 0.03). Conclusion: Findings underscore the need for heightened awareness, screening, and intervention efforts targeting pregabalin misuse within SUD treatment. Further research should focus on longitudinal studies to elucidate pregabalin dependence’s trajectory.

Background: The thyroid hormone is so essential that it is involved in the functioning of all the body systems, especially in the development of the brain in fetal life. The World Health Organization has estimated that around 2 billion individuals are suffering from thyroid disorders. Hence, it is essential to identify and diagnose hypothyroid patients so that the treatment strategy can be started at the earliest. Aims and Objectives: The present study aimed to find out the peripheral nerve conduction velocity, range, and degree of movement of joints in newly diagnosed hypothyroid women and compare them with those of normal euthyroid women. Materials and Methods: The present study was a case–control study conducted from July 2015 to March 2016. A total of 50 cases of newly diagnosed hypothyroid women and 50 age-matched euthyroid women were part of the study after obtaining written and informed consent. Thyroid estimation was performed in the Clinical Biochemistry Department by the ELISA method, and nerve conduction studies were performed in the Neurology Department. Results: The age and height of the participants were not statistically significant. Weight and body mass index were significantly higher in the cases when compared to the control group. Sensory and motor conduction velocities of the right median nerve are significantly less in these cases when compared to control group participants. Sensory and motor conduction velocities of the right ulnar nerve are significantly less in these cases when compared to control group participants. Sensory and motor conduction velocities of the left median nerve are significantly less in these cases when compared to control group participants. Sensory and motor conduction velocities of the left ulnar nerve are significantly less in these cases when compared to control group participants. The goniometric parameters (right and left sides) of the cases and control group participants were not significantly different. Conclusion: Hypothyroid women have a delay in peripheral nerve conduction velocities, including sensory and motor components, and the degree and range of movements of limb joints were not affected. A nerve conduction study may be utilized as a routine screening test for hypothyroid individuals so that hormone replacement therapy can be instituted at the earliest.

Background: It is frequently observed that dental students require so many consents to manage medically compromised patients, especially cardiovascular patients with periodontitis requiring dental treatment. Aims and Objectives: The present study aimed to assess the dental students’ knowledge, attitudes, and practices regarding the management of cardiovascular disease (CVD) patients with periodontitis requiring dental treatment. Material and Methods: The cross-sectional study was conducted among 611 dental undergraduate and postgraduate students (branches of Periodontology, Oral and Maxillofacial Surgery, Oral Medicine and Radiology, Endodontics, Prosthodontics, and Public Health and Dentistry) of central Gujrat. Self-administered structured questionnaires with 23 questions were distributed in pen-and-paper physical format. Statistical analysis for descriptive statistics like frequency, percentage, mean, standard deviation, confidence interval, one-way analysis of variance, post hoc test for multiple comparisons, Fisher’s exact test, and Pearson’s correlation has been done by MS Excel and STATA/IC-13. Results: As per the post hoc test, both groups of students have significantly different knowledge (-4.20210*, P = 0.028) and their practices (0.68632, P = 0.968) but no significant difference between their attitudes (-6.22828, P = 0.089). According to the Pearson correlation test, a weak positive/no relationship between knowledge, attitudes, and practice is reported in both study groups. There is a weak positive relation between knowledge and attitudes (0.270) and between knowledge and practices (0.121), and a similar relationship between their attitudes and practices (0.172) was observed in both groups. Conclusion: Correct knowledge, attitudes, and practices regarding dental management of CVD patients with periodontitis can reduce medical consent to improve the treatment quality of dental students.

Conventional thermally processed apple juices are nutritionally depleted because the heat sensitivity degrades the bioactive compounds that comprise them. This study proposed a non-thermal technique, hydrodynamic cavitation (HC), to preserve the nutritional content and prevent the loss of bioactive components in apple juice. In addition, the effect of hydrodynamic cavitation on the physicochemical, nutrition, and enzyme inactivation of freshly expressed apple juice has been studied. The design expert software has been used for process optimization, while fuzzy logic was applied for sensory. Hydrodynamic cavitation has been used on freshly extracted apple juice with inlet pressure in the range of (34.47–103.421 kPa) for a treatment time of (0–30 min). The apple juice was treated thermally at 90 °C for 2.5 min to compare the cavitation results. The settling of particles in the cavitation sample was 7%, which was lower than the heat-treated sample (10%) and untreated control sample (39%) and had a noticeable effect on the cloud value and stability of the apple juice. The HC treatment reduces the particle size of fresh apple juice from 8934.09 nm to 1112 nm, resulting in a homogenizing effect, a decrease in viscosity, and improved juice stability. Hydrodynamic cavitation reduced the antioxidant activity from 0.4987 mg GAE mL−1 (control) to 0.3951 mg GAE mL−1 yet retained better activity than the heat-treated apple juice (0.3489 ± 0.34 mg GAE mL−1) with microbial log reduction of 0.9 at 103.42 kPa treated for 30 min. After 15 days of storage at 4 °C, HC-treated juice had higher quality features and nutrient retention than heat-treated apple juice.

Effect of hydrodynamic cavitation (HC) processing on pH, °brix, separation index, viscosity and color properties, retention of nutritional bioactive compounds (Vitamin-C, total phenolics, and antioxidant), and inactivation of enzyme pectin methyl esterase (PME) in freshly expressed juice from Brazilian oranges was investigated. HC at 4 bar pressures with a treatment time of 0, 10, 20, 30, 40, 50, 60, and 90 min at low temperatures (42 °C) were studied. There was no significant change in the values of pH, and TSS was noted in HC-treated juices. Further decreased flow behavior index while increased values of flow consistency index were recorded for the juice treated with HC showing a significant physical modification of the juice. Degradation and loss in vitamin C and total phenolics were observed when juices were HC-treated for a longer time. Therefore, it was concluded that HC could be used as a non-thermal method for improving the stability and physicochemical properties of Brazilian orange juice.

The conventional thermal treatment causes chemical modifications to milk constituents such as protein denaturation, loss of vitamins and flavoring compounds, depression at freezing point, and nonenzymatic browning, which may result in adverse changes to the flavor, color, and nutritional value of milk. This review looks into the emerging non-thermal processing techniques such as high-pressure processing (HPP), pulsed electric field (PEF), ultrasonication and hydrodynamic, UV-irradiation and plasma technology, cavitation, and their effects on milk components and bioactive compounds. For consumer acceptability and safety, simultaneous and crucial needs exist: microbial safety, fresh like quality and preservation of bioactive compounds. Technologies like HPP and PEF have been capable of achieving microbial reduction with moderate thermal inputs. Ultrasonication and hydrodynamic cavitation have the dual functions of deactivating microorganisms and homogenizing, and plasma and UV-C radiation could ensure minimal loss of heat-sensitive components. These processing techniques could be an alternative to pasteurization and sterilization of milk with assured microbial inactivation and maximal retention of nutrients in dairy.

Abstract Fresh apple juice is one of the most popular and consumed juice, owing to its pleasant taste, natural flavour and nutritional richness. Regular consumption of apple juice is associated with reducing the risk of cancer, cardiovascular related diseases, asthma and diabetes. However, the shelf life of apple juice is limited by detrimental effect of enzymes. Due to the demand of wholesome nutritious product, there arises a need for adoption of novel non-thermal techniques as they help to retain the nutritional content and at the same time aid in improving the shelf life as compared to the thermal treatment. High pressure processing (HPP), pulsed electric field (PEF), ultrasound, pulsed light, UV, high-pressure homogenization (HPH) and hydrodynamic cavitation (HC) are all examples of novel procedures tested and tried for the better retention of nutritional and phytochemical composition in apple juice. This study aimed to find the influence of these mechanisms on the quality and composition of apple juice. Apple juice processing has been successfully examined using non-thermal techniques. These exhibited promising results in terms of minimising physical, chemical, enzymatic and microbial deterioration of the apple juice while still retaining a high percentage of nutritious components. Though all the non-thermal process require a hurdle approach for inactivation of enzymes, HC can be a better alternative in terms of operating costs and ease in handling the bulk volumes of juice. Graphical Abstract

The World Health Organization (WHO) and American Psychiatric Association (APA) have recognised premenstrual dysphoric disorder (PMDD) as an independent diagnostic entity, legitimising the distress and socio-occupational impairment experienced by affected women. However, the biological validity of this diagnosis remains inexplicit. This illness has also been criticised for a feminist-led, sympathetic reaction to the modern cultural challenges of urban, literate, employed, high-functioning women. This article systematically reviews existing literature on PMDD using the criteria established by Robins and Guze for the validity of a psychiatric diagnosis (clinical description, laboratory study, exclusion of other disorders, follow-up study, and family study). Despite the early recognition of premenstrual syndrome (PMS) in the 1950s, the research has encountered challenges due to two groups of proponents viewing it with psychologising bias and medicalising bias. PMDD is currently understood as the most severe form of PMS, characterised by the presence of psychological features. Recent evidence suggests that PMDD perhaps has neurodevelopmental underpinnings (attention deficit hyperactive disorder, adverse childhood experiences) affecting the fronto-limbic circuit that regulates the emotions. In addition, the affected individuals exhibit an increased sensitivity to gonadal hormonal fluctuations as observed during premenstrual, pregnancy, and perimenopausal phases of life. The prevalence is comparable between high-income countries and low- and middle-income countries (LAMIC), refuting the notion that it mostly affects modern women. Instead, a greater prevalence is observed in LAMIC. Despite the fact that educated women possess knowledge regarding the importance of getting help, there is a prevalent issue of inadequate help-seeking behaviour. This can be attributed to the perception of seeking help as an isolating experience, which is influenced by profound internalised stigma and discrimination in the workplace. Future studies must aim to develop culturally validated assessment tools and more research to understand the life course of the illness, in addition to systematically examining for more biological validators (animal models, genetics, imaging, neurotransmitters).

Hydrodynamic cavitation (HC) is the process of bubbles formation, expansion, and violent collapse, which results in the generation of high pressures in the order of 100–5000 bar and temperatures in the range of 727–9727 °C for just a fraction of seconds. Increasing consumer demand for high-quality foods with higher nutritive values and fresh-like sensory attributes, food processors, scientists, and process engineers are pushed to develop innovative and effective non-thermal methods as an alternative to conventional heat treatments. Hydrodynamic cavitation can play a significant role in non-thermal food processing as it has the potential to destroy microbes and reduce enzyme activity while retaining essential nutritional and physicochemical properties. As hydrodynamic cavitation occurs in a flowing liquid, there is a decrease in local pressure followed by its recovery; hence it can be used for liquid foods. It can also be used to create stable emulsions and homogenize food constituents. Moreover, this technology can extract food constituents such as polyphenols, essential oils, pigments, etc., via biomass pretreatment, cell disruption for selective enzyme release, waste valorization, and beer brewing. Other applications related to food production include water treatment, biodiesel, and biogas production. The present review discusses the application of HC in the preservation, processing, and quality improvement of food and other related applications. The reviewed examples in this paper demonstrate the potential of hydrodynamic cavitation with further expansion toward the scaling up, which looks at commercialization as a driving force.

Background The prostate tumor microenvironment (TME) is immunosuppressive, with few effector T cells and enrichment of inhibitory immune populations, leading to limited responses to treatments such as immune checkpoint therapies (ICTs). The immune composition of the prostate TME differs across soft tissue and bone, the most common site of treatment-refractory metastasis. Understanding immunosuppressive mechanisms specific to prostate TMEs will enable rational immunotherapy strategies to generate effective antitumor immune responses. Daratumumab (anti-CD38 antibody) and edicotinib (colony-stimulating factor-1 receptor (CSF-1R) inhibitor) may alter the balance within the prostate TME to promote antitumor immune responses.Hypothesis Daratumumab or edicotinib will be safe and will alter the immune TME, leading to antitumor responses in localized prostate cancer.Patients and methods In this presurgical study, patients with localized prostate cancer received 4 weekly doses of daratumumab or 4 weeks of daily edicotinib prior to radical prostatectomy (RP). Treated and untreated control (Gleason score ≥8 in prostate biopsy) prostatectomy specimens and patient-matched pre- and post-treatment peripheral blood mononuclear cells (PBMCs) and bone marrow samples were evaluated. The primary endpoint was incidence of adverse events (AEs). The secondary endpoint was pathologic complete remission (pCR) rate.Results Twenty-five patients were treated (daratumumab, n=15; edicotinib, n=10). All patients underwent RP without delays. Grade 3 treatment-related AEs with daratumumab occurred in 3 patients (12%), and no ≥grade 3 treatment-related AEs occurred with edicotinib. No changes in serum prostate-specific antigen (PSA) levels or pCRs were observed. Daratumumab led to a decreased frequency of CD38+ T cells, natural killer cells, and myeloid cells in prostate tumors, bone marrow, and PBMCs. There were no consistent changes in CSF-1R+ immune cells in prostate, bone marrow, or PBMCs with edicotinib. Neither treatment induced T cell infiltration into the prostate TME.Conclusions Daratumumab and edicotinib treatment was safe and well-tolerated in patients with localized prostate cancer but did not induce pCRs. Decreases in CD38+ immune cells were observed in prostate tumors, bone marrow, and PBMCs with daratumumab, but changes in CSF-1R+ immune cells were not consistently observed with edicotinib. Neither myeloid-targeted agent alone was sufficient to generate antitumor responses in prostate cancer; thus, combinations with agents to induce T cell infiltration (eg, ICTs) will be needed to overcome the immunosuppressive prostate TME.

Abstract The surging demand of value-added products has steered the transition of laboratory microbes to microbial cell factories (MCFs) for facilitating production of large quantities of important native and non-native biomolecules. This shift has been possible through rewiring and optimizing different biosynthetic pathways in microbes by exercising frameworks of metabolic engineering and synthetic biology principles. Advances in genome and metabolic engineering have provided a fillip to create novel biomolecules and produce non-natural molecules with multitude of applications. To this end, numerous MCFs have been developed and employed for production of non-natural nucleic acids, proteins and different metabolites to meet various therapeutic, biotechnological and industrial applications. The present review describes recent advances in production of non-natural amino acids, nucleic acids, biofuel candidates and platform chemicals.

Anti-CTLA4 therapy has not been comprehensively explored for the treatment of metastatic renal cell carcinoma (mRCC). Here, in a pilot study of anti-CTLA4 therapy with or without cryoablation in mRCC, the authors report that the combination is feasible and enhances immune infiltration in patients with metastatic clear cell histology.

Scientific collaborations among nations to address common problems and to build international partnerships as part of science diplomacy is a well-established notion. The international flow of people and ideas has played an important role in the advancement of the ‘Sciences’ and the current pandemic scenario has drawn attention towards the genuine need for a stronger role of science diplomacy, science advice and science communication. In dealing with the COVID-19 pandemic, visible interactions across science, policy, science communication to the public and diplomacy worldwide have promptly emerged. These interactions have benefited primarily the disciplines of knowledge that are directly informing the pandemic response, while other scientific fields have been relegated. The effects of the COVID-19 pandemic on scientists of all disciplines and from all world regions are discussed here, with a focus on early-career researchers (ECRs), as a vulnerable population in the research system. Young academies and ECR-driven organisations could suggest ECR-powered solutions and actions that could have the potential to mitigate these effects on ECRs working on disciplines not related to the pandemic response. In relation with governments and other scientific organisations, they can have an impact on strengthening and creating fairer scientific systems for ECRs at the national, regional, and global level.

Granulomatous/sarcoid-like lesions have been reported in patients treated with immune checkpoint inhibitors (ICIs). Here the authors report the occurrence of “nodal immune flare”, an apparent radiological cancer progression in the nodes characterized by the absence of cancer and the presence of non-caseating granulomas, in patients with non-small cell lung cancer following neoadjuvant ICI treatment.

Abstract Marfan syndrome and related disorders are a group of heritable connective tissue disorders and share many clinical features that involve cardiovascular, skeletal, craniofacial, ocular, and cutaneous abnormalities. The majority of affected individuals have aortopathies associated with early mortality and morbidity. Implementation of targeted gene panel next-generation sequencing in these individuals is a powerful tool to obtain a genetic diagnosis. Here, we report on clinical and genetic spectrum of 53 families from India with a total of 83 patients who had a clinical diagnosis suggestive of Marfan syndrome or related disorders. We obtained a molecular diagnosis in 45/53 (85%) index patients, in which 36/53 (68%) had rare variants in FBN1 (Marfan syndrome; 63 patients in total), seven (13.3%) in TGFBR1/TGFBR2 (Loeys–Dietz syndrome; nine patients in total) and two patients (3.7%) in SKI (Shprintzen–Goldberg syndrome). 21 of 41 rare variants (51.2%) were novel. We did not detect a disease-associated variant in 8 (15%) index patients, and none of them met the Ghent Marfan diagnostic criteria. We found the homozygous FBN1 variant p.(Arg954His) in a boy with typical features of Marfan syndrome. Our study is the first reporting on the spectrum of variants in FBN1, TGFBR1, TGFBR2, and SKI in Indian individuals.

Aims and Method: This paper aims to review the recent literature regarding factors influencing the frequency and number of sessions during a course of electroconvulsive therapy (ECT) for different psychiatric disorders. We systematically reviewed English-language papers of clinical trials of ECT published since the year 2000 in terms of frequency and number of sessions of ECT. Results: None of the 30 studies meeting our inclusion criteria were specifically designed to study frequency or number of sessions of ECT. A preliminary inference may be drawn regarding the number of sessions from the information available in these papers. For depression, patients receiving brief-pulse ECT needed fewer sessions than those receiving ultra-brief ECT when these were delivered at 8-times the threshold with unilateral electrode placement or at 2.5-times the threshold with bilateral placement. For schizophrenia, those receiving bifrontal ECT and ECT at 4-times the threshold-level stimulus needed fewer sessions than those receiving bitemporal ECT and 2-times the threshold-level stimulus, respectively. There were no clinical trials of the frequency of ECT sessions.Clinical Implications: A s there is a dearth of studies specifically examining frequency and number of ECT sessions, broad recommendations from professional bodies should continue to guide practice.

Water scarcity is a major challenge in the agriculture industry, and traditional irrigation methods are often wasteful and inefficient. To address this challenge, a smart solar irrigation system that uses loT and Artificial Neural Network (ANN) algorithms can optimize water usage for agriculture. The system can provide automated irrigation, improve crop yields, and reduce water consumption. This paper proposes a design and implementation methodology of a smart solar irrigation system using loT and ANN algorithms. The system includes solar panels, a water pump, a water storage tank, sensors, loT devices, and ANN algorithms. The system is designed to automate the irrigation process by controlling the water pump based on the data collected from the sensors.

This research introduces an approach to detect malware attacks using blockchain technology that integrates signature-based and behavioralbased methods. The proposed system uses a decentralized blockchain network to share and store malware signatures and behavioral patterns. This enables faster and more efficient detection of new malware files. The signature-based method involves storing the signatures in the blockchain and the sharing of the signature of malware files among the user nodes of the p2p blockchain network, while the behavioral-based approach analyzes the behavior and actions of files in a separate virtualized environment to identify suspicious patterns. This system addresses the limitations of conventional signature-based methods, which can be evaded by polymorphic malware, and behavioral-based methods, which may generate false positives. The results of the evaluation indicate that the proposed system achieves high detection rates while maintaining low false positives. Overall, the proposed system offers an effective and efficient approach to malware detection by utilizing the strengths of both signature-based and behavioral-based methods and utilizing the security and transparency benefits of blockchain technology.

Organ-on-a-chip (OOAC) is an emerging technology based on microfluid platforms and in vitro cell culture that has a promising future in the healthcare industry. The numerous advantages of OOAC over conventional systems make it highly popular. The chip is an innovative combination of novel technologies, including lab-on-a-chip, microfluidics, biomaterials, and tissue engineering. This paper begins by analyzing the need for the development of OOAC followed by a brief introduction to the technology. Later sections discuss and review the various types of OOACs and the fabrication materials used. The implementation of artificial intelligence in the system makes it more advanced, thereby helping to provide a more accurate diagnosis as well as convenient data management. We introduce selected OOAC projects, including applications to organ/disease modelling, pharmacology, personalized medicine, and dentistry. Finally, we point out certain challenges that need to be surmounted in order to further develop and upgrade the current systems.

Pomegranate peel (PP) is one of the interesting agri-food by-products because of its abundant bioactive phytochemicals. However, the bioactivity of valuable compounds is affected due to the extraction method used. A pulsed ultrasound-assisted extraction (PUAE) was carried out to intensify the extraction efficacy with reduced power and time. Influence of several process variables viz. peel solids/ solvent ratio, sonication power, duty cycle, and extraction time was studied using empirical quadratic models followed by multicriterial numerical optimization with respect to face-centered composite design. Power-duty cycle combination was found to be most significant (p

Abstract Background Despite significant advancements in healthcare technology, digital health solutions – especially those for serious mental illnesses – continue to fall short of their potential across both clinical practice and efficacy. The utility and impact of medicine, including digital medicine, hinges on relationships, trust, and engagement, particularly in the field of mental health. This paper details results from Phase 1 of a two-part study that seeks to engage people with schizophrenia, their family members, and clinicians in co-designing a digital mental health platform for use across different cultures and contexts in the United States and India. Methods Each site interviewed a mix of clinicians, patients, and their family members in focus groups (n = 20) of two to six participants. Open-ended questions and discussions inquired about their own smartphone use and, after a demonstration of the mindLAMP platform, specific feedback on the app's utility, design, and functionality. Results Our results based on thematic analysis indicate three common themes: increased use and interest in technology during coronavirus disease 2019 (COVID-19), concerns over how data are used and shared, and a desire for concurrent human interaction to support app engagement. Conclusion People with schizophrenia, their family members, and clinicians are open to integrating technology into treatment to better understand their condition and help inform treatment. However, app engagement is dependent on technology that is complementary – not substitutive – of therapeutic care from a clinician.

Background Pegylated arginine deiminase (ADI-PEG 20) is a metabolism-based strategy that depletes arginine, resulting in tumoral stress and cytotoxicity. Preclinically, ADI-PEG 20 modulates T-cell activity and enhances the therapeutic efficacy of programmed death-1 (PD-1) inhibition. Methods A phase 1b study, including a dose-escalation cohort and an expansion cohort, was undertaken to explore the effects of ADI-PEG 20 in combination with pembrolizumab, an anti-PD-1 antibody, for safety, pharmacodynamics, and response. CD3 levels and programmed death-ligand 1 (PD-L1) expression were assessed in paired biopsies collected prior to and after ADI-PEG 20 treatment but before pembrolizumab. Results Twenty-five patients, nine in the dose-escalation cohort and sixteen in the expansion cohort, were recruited. Treatment was feasible with adverse events consistent with those known for each agent, except for Grade 3/4 neutropenia which was higher than expected, occurring in 10/25 (40%) patients. Mean arginine levels were suppressed for 1–3 weeks, but increased gradually. CD3+ T cells increased in 10/12 (83.3%) subjects following ADI-PEG 20 treatment, including in three partial responders (p = .02). PD-L1 expression was low and increased in 3/10 (30%) of subjects. Partial responses occurred in 6/25 (24%) heavily pretreated patients, in both argininosuccinate synthetase 1 proficient and deficient subjects. Conclusions The immunometabolic combination was safe with the caveat that the incidence of neutropenia might be increased compared with either agent alone. ADI-PEG 20 treatment increased T cell infiltration in the low PD-L1 tumor microenvironment. The recommended phase 2 doses are 36 mg/m2 weekly for ADI-PEG 20 and 200 mg every 3 weeks for pembrolizumab.

The COVID-19 pandemic has created opportunities for innovation, ingenuity, and system reengineering. The next big investment in health care should be intentional and embedded partnerships between clinicians, designers, and architects who can collaborate to help solve health care’s greatest challenges.

Access to mental health care has significant disparities due to treatment gap, more so particularly for the remotely residing, physically vulnerable, aging populations. Adoption of technology will enable more people to receive specialty care addressing distance, transportation and cost-related barriers to treatment engagement from the comfort of home. Telemedicine has been regarded as “electronic personal protective equipment” by reducing the number of physical contacts and risk contamination for patients during COVID-19 crisis. This review aimed to give a broad view of patients’ perception of the use of telepsychiatry in terms of clinical outcome, cost-effectiveness, and solutions to address patients’ challenges with the adoption of technology. Over the years, telepsychiatry, both in synchronous and asynchronous modalities, had shown to improve patients’ adherence to treatment, follow-up rates, and clinical symptoms, overcome stigma and discrimination, and save cost expenses accessing health care with better satisfaction and usability outcomes. Its utility is widespread such as in delivering care emergency evaluation, crisis intervention, conducting neuropsychological assessments, psychotherapy, promoting lifestyle modification, enhancing self-efficacy, and overcoming patients’ linguistic and cultural barriers to care. However, patients’ privacy and confidentiality and psychiatrists’ legal liability remain as matter of major concern in digital platform. To keep up with the pace of technology and patients’ expectations, a more agile approach is essential to develop, improve, and evaluate telepsychiatric interventions.

Prostate cancer (PCa) remains the second-leading cause of cancer-related deaths in American men with an estimated mortality of more than 26,000 in 2016 alone. Aggressive and metastatic tumors are treated with androgen deprivation therapies (ADT); however, the tumors acquire resistance and develop into lethal castration resistant prostate cancer (CRPC). With the advent of better therapeutics, the incidences of a more aggressive neuroendocrine prostate cancer (NEPC) variant continue to emerge. Although de novo occurrences of NEPC are rare, more than 25% of the therapy-resistant patients on highly potent new-generation anti-androgen therapies end up with NEPC. This, along with previous observations of an increase in the number of such NE cells in aggressive tumors, has been suggested as a mechanism of resistance development during prostate cancer progression. Dovitinib (TKI-258/CHIR-258) is a pan receptor tyrosine kinase (RTK) inhibitor that targets VEGFR, FGFR, PDGFR, and KIT. It has shown efficacy in mouse-model of PCa bone metastasis, and is presently in clinical trials for several cancers. We observed that both androgen receptor (AR) positive and AR-negative PCa cells differentiate into a NE phenotype upon treatment with Dovitinib. The NE differentiation was also observed when mice harboring PC3-xenografted tumors were systemically treated with Dovitinib. The mechanistic underpinnings of this differentiation are unclear, but seem to be supported through MAPK-, PI3K-, and Wnt-signaling pathways. Further elucidation of the differentiation process will enable the identification of alternative salvage or combination therapies to overcome the potential resistance development.

Gulf War Illness (GWI) is a multisymptom disorder including widespread chronic pain, fatigue and gastrointestinal problems. The objective of this study was to examine the low glutamate diet as a treatment for GWI. Forty veterans with GWI were recruited from across the US. Outcomes included symptom score, myalgic score, tender point count, dolorimetry and the Chalder Fatigue Scale. Subjects were randomized to the low glutamate diet or a wait-listed control group, with symptom score being compared after one month. Subjects then went onto a double-blind, placebo-controlled crossover challenge with monosodium glutamate (MSG)/placebo to test for return of symptoms. Symptom score was compared between diet intervention and wait-listed controls with an independent t-test and effect size was calculated with Cohen’s d. Change scores were analyzed with Wilcoxon Signed Rank tests. Crossover challenge results were analyzed with General Linear Models and cluster analysis. The diet intervention group reported significantly less symptoms (p = 0.0009) than wait-listed controls, with a very large effect size, d = 1.16. Significant improvements in average dolorimetry (p = 0.0006), symptom score, tender point number, myalgic score and the Chalder Fatigue Scale (all p < 0.0001) were observed after the 1-month diet. Challenge with MSG/placebo resulted in significant variability in individual response. These results suggest that the low glutamate diet can effectively reduce overall symptoms, pain and fatigue in GWI, but differential results upon challenge suggest that other aspects of the diet, or underlying differences within the population, may be driving these changes. Future research is needed to identify potential nutrient effects, biomarkers, and underlying metabolic differences between responders and non-responders.

There is an emerging link between the accumulation of iron in the brain and abnormal tau pathology in a number of neurodegenerative disorders, such as Alzheimer’s disease (AD). Studies have demonstrated that iron can regulate tau phosphorylation by inducing the activity of multiple kinases that promote tau hyperphosphorylation and potentially also by impacting protein phosphatase 2A activity. Iron is also reported to induce the aggregation of hyperphosphorylated tau, possibly through a direct interaction via a putative iron binding motif in the tau protein, facilitating the formation of neurofibrillary tangles (NFTs). Furthermore, in human studies high levels of iron have been reported to co-localize with tau in NFT-bearing neurons. These data, together with our own work showing that tau has a role in mediating cellular iron efflux, provide evidence supporting a critical tau:iron interaction that may impact both the symptomatic presentation and the progression of disease. Importantly, this may also have relevance for therapeutic directions, and indeed, the use of iron chelators such as deferiprone and deferoxamine have been reported to alleviate the phenotypes, reduce phosphorylated tau levels and stabilize iron regulation in various animal models. As these compounds are also moving towards clinical translation, then it is imperative that we understand the intersection between iron and tau in neurodegeneration. In this article, we provide an overview of the key pathological and biochemical interactions between tau and iron. We also review the role of iron and tau in disease pathology and the potential of metal-based therapies for tauopathies.

Background: Sida L., is a medicinally important genus, the species of which are widely used in traditional systems of medicine in India. Pharmacologically, roots are known for anti-tumor, anti-HIV, hepatoprotective, and many other properties. Phenolic antioxidants help in reducing oxidative stress occurring during treatment of such diseases. Objective: The study aimed to evaluate and compare polyphenol contents and antioxidant properties of eight selected species of Sida from Western Ghats, India. Materials and Methods: Methanolic root extracts (10% w/v) of Sida species, viz., S. acuta, S. cordata, S. cordifolia, S. indica, S. mysorensis, S. retusa, S. rhombifolia, and S. spinosa were analyzed. Results: Sida cordifolia possessed highest total phenolic content (TPC: 1.92 ± 0.10 mg Caffeic Acid Equivalent/g and 2.13 ± 0.11 mg Tannic Acid Equivalant/g), total flavonoid content (TF: 2.60 ± 0.13 mg Quercetin Equivalent/g) and also possessed highest antioxidant activities in 2,2-diphenylpicrylhydrazyl (DPPH) radical scavenging (51.31 ± 2.57% Radical Scavenging Activity, (RSA); Trolox Equivalent Antioxidant Capacity: 566.25 ± 28.31μM; Ascorbic acid Equivalent Antioxidant Capacity: 477.80 ± 23.89 μM) and Ferric Reducing Antioxidant Power assays (TEAC: 590.67 ± 29.53 μM; AEAC: 600.67 ± 30.03 μM). Unlike DPPH and Ferric Reducing Antioxidant Power (FRAP) activity, 2, 2Ͳ-Azinobis (3-ethyl Benzo Thiazoline-6-Sulfonic acid) ABTS + antioxidant activity was highest in S. indica (TEAC: 878.44 ± 43.92 μM; AEAC 968.44 ± 48.42 μM). It was significant to note that values of AEAC (μM) for all the antioxidant activities analyzed were higher than that of TEAC. Conclusion: The high contents of phenolic compounds in the root extracts of selected Sida species have direct correlation with their antioxidant properties. Conclusively, roots of S. cordifolia can be considered as the potential source of polyphenols and antioxidants.

Middle Interhemispheric variant (MIH) is a rare subtype of holoprosencephaly (HPE), also known as syntelencephaly. We present a case of MIH, which was diagnosed as an interhemispheric cyst on antenatal sonography at 19 weeks, but later diagnosed as MIH variant of holoprosencephaly after a postabortal MRI and perinatal autopsy.

Neuroblastic tumours are common in childhood and adrenal glands are the most common site. Head and neck ganglioneuroblastomas are extremely rare and nose is a very uncommon site for a ganglioneuroblastoma. The management of this primitive sympathogonic tumour may vary depending on the age of the patient and stage of the tumour. We present a middle-aged man with a ganglioneuroblastoma of skull base, management of this tumour and a review of literature.

[This corrects the article DOI: 10.1057/s41599-021-00944-1.].

Scientific collaborations among nations to address common problems and to build international partnerships as part of science diplomacy is a well-established notion. The international flow of people and ideas has played an important role in the advancement of the 'Sciences' and the current pandemic scenario has drawn attention towards the genuine need for a stronger role of science diplomacy, science advice and science communication. In dealing with the COVID-19 pandemic, visible interactions across science, policy, science communication to the public and diplomacy worldwide have promptly emerged. These interactions have benefited primarily the disciplines of knowledge that are directly informing the pandemic response, while other scientific fields have been relegated. The effects of the COVID-19 pandemic on scientists of all disciplines and from all world regions are discussed here, with a focus on early-career researchers (ECRs), as a vulnerable population in the research system. Young academies and ECR-driven organisations could suggest ECR-powered solutions and actions that could have the potential to mitigate these effects on ECRs working on disciplines not related to the pandemic response. In relation with governments and other scientific organisations, they can have an impact on strengthening and creating fairer scientific systems for ECRs at the national, regional, and global level.