Total Synthesis and Revision of Stereochemistry of a Natural Benzo[g]isochromene Stereodiad Isolated from Rubia philippinensis.

This study presents a total synthesis and revision of the stereochemical configuration of the conformationally flexible natural product benzo[g]isochromene stereodiad alongside its diastereomeric counterparts. The highlights of the synthesis are the TiCl4-mediated diastereoselective aldol reaction, Pd-catalyzed lactonization, and Schmidt glycosidation. Our efforts using total synthesis disclosed herein proved that a previously assigned structure required revision.

Template Routed Patient-Specific Implant for 1-Stage Cranioplasty.

BACKGROUND AND OBJECTIVES: Cranial reconstruction presents a significant challenge in cases involving pathologies with skull invasion, and various techniques have been used, including the intraoperative shaping of titanium mesh and the manual sculpting of bone cement serving as surrogates for the excised bone graft. In the context of prefabricated patient-specific implants (PSIs) for cranioplasty, precise surgical execution of craniotomies is paramount. This ensures optimal congruity between the implant and the defect created during the craniotomy, leading to a successful single-stage procedure encompassing both bone removal and reconstruction. This article presents a meticulous method for achieving such high-fidelity craniotomy and subsequent cranioplasty using PSIs in a single-stage surgery. METHODS: The procedure was implemented for 2 cases of meningiomas with osseous invasion. Through meticulous preoperative planning, the craniotomy template and implant were designed using computer-assisted design and manufactured on a 3-dimensional printer using the patient's computed tomography scans. Intraoperative fabrication of sterile polymethyl methacrylate replicas was achieved through the creation of silicone molds and subsequent injection molding techniques. Predesignated screw holes facilitated neuronavigation-assisted positioning of the template, aligning it accurately with the target site using registration points. Mini-screws firmly secured the template to the skull. Guided by the template, a craniotomy router performed the bone resection. On completion, the implant was affixed into place using plates and screws. RESULTS: This technique demonstrably facilitated a cost-effective, streamlined and precise application of prefabricated PSIs within a single-stage craniotomy-cranioplasty procedure. Subjective patient reports indicated high levels of satisfaction with the outcome. CONCLUSION: The template routed patient-specific implant 1-stage cranioplasty technique refines previous approaches through precise template localization on the skull, enabling an accurate craniotomy to match a prefabricated PSI. This single-stage procedure rivals hand-shaped methods in aesthetics and compares with the outcomes of 2-stage PSI cranioplasties. Additional studies are needed to validate our results.

Laparoscopic subtotal cholecystectomy in difficult gallbladder: Our experience in a tertiary care center.

Backgrounds/Aims: Open cholecystectomy is becoming obsolete and laparoscopic cholecystectomy has become the treatment of choice in gallstone diseases. Difficult gallbladders are encountered whenever there is a frozen calot's triangle, obliterated cystic plate, or both. Rather than converting to open procedure, there has been a growing preference for laparoscopic subtotal cholecystectomy (LSC) during difficult gallbladders. This study aimed to assess the advantages, indications, and viability of LSC in difficult gallbladders. Methods: The study included patients undergoing laparoscopic cholecystectomy in NIMS Hospital, Jaipur, from January 2021 to January 2023. Data of the patients who underwent LSC for difficult gallbladders included demographics, comorbidities, operative time, conversion to open cholecystectomy, length of hospital stay, and complications. LSC was classified into three types depending on the part of the gallbladder remnant. Results: A total of 728 patients underwent laparoscopic cholecystectomy. Among them, 41 patients (5.6%) were attempted for LSC. However, one patient was converted to an open procedure and the rest 40 underwent LSC. LSC was divided into 3 types, 4 patients underwent LSC type I, 34 patients underwent type II, and 2 patients type III. The average operating time and postoperative length of hospital stay were 86.2 minutes and 2.1 days, respectively. Two patients had surgical site infection. No patient had a bile leak and none required intensive care unit care. Conclusions: LSC is a safe and feasible option for use in difficult gallbladders.

Experimental and numerical analysis of the thermal performance of pebble solar thermal collector.

In this work, pebbles of higher specific heat than the conventional absorber materials like aluminium or copper are proposed as a absorber in the solar flat plate collector. The proposed collector are integrated into the building design and constructed with masonry. Tests were conducted by varying the operating parameters which influence its performance, like the flow rate of the heat-absorbing medium, and the tilt of the collector using both coated and uncoated pebbles. The maximum temperature difference that could be measured for a conventional absorber was approximately 8 °C for a flow rate of 0.6 L/min. While for a coated and uncoated absorber, it was 7 °C and 5.5 °C respectively. This difference decreased with an increase in flow rates from 0.6 L/min to 1.2 L/min. For all the flow rates, it was observed that the average difference in efficiency between the coated and the conventional absorber collector is 5.82 %, while the difference between the coated and uncoated absorber collector is 15.68 %. Thus, it is very much evident that by replacing the conventional absorber with the proposed coated pebble absorber, the overall loss in efficiency is just 5.82 %, but the advantages are enormous. Along with the experimental study, numerical analysis was also carried out with CFD modeling. The numerical results agreed well with experimental results with the least error. Therefore, CFD simulation can be further used to optimize the design of the collector.

How best can we name the channels seen in the setting of deficient ventricular septation?

Surgical repair of channels between the ventricles is enhanced when the surgeon knows precisely where to place a patch, or baffle, so as to restore septal integrity. The paediatric cardiologist should provide the necessary information. Communication will be enhanced if the same words are used to account for the structures in question. Currently, however, the same term, namely "ventricular septal defect," is used to account for markedly different areas within the heart. Closure of perimembranous defects found in hearts with concordant or discordant ventriculo-arterial connections restores the integrity of the ventricular septum, at the same time separating the systemic and pulmonary blood streams. When both arterial trunks arise from the right ventricle, in contrast, the surgeon when placing a baffle so as to separate the blood streams, does not close the channel most frequently described as the "ventricular septal defect." In this review, we show that the perimembranous lesions as found in hearts with concordant or discordant ventriculo-arterial connections are the right ventricular entrances to the areas subtended beneath the hinges of the leaflets of the aortic or pulmonary valves. When both arterial trunks arise from the right ventricle, and the channel between the ventricles is directly subaortic, then the channel termed the "ventricular septal defect" is the left ventricular entrance to the comparable space subtended beneath the aortic root. We argue that recognition of these fundamental anatomical differences enhances the appreciation of the underlying morphology of the various lesions that reflect transfer, during cardiac development, of the aortic root from the morphologically right to the morphologically left ventricle.

CpsA mediates infection of recruited lung myeloid cells by Mycobacterium tuberculosis.

Mycobacterium tuberculosis (Mtb) possesses an arsenal of virulence factors to evade host immunity. Previously, we showed that the Mtb protein CpsA, which protects Mtb against the host NADPH oxidase, is required in mice during the first 3 weeks of infection but is thereafter dispensable for full virulence. Using flow cytometry, we find that ΔcpsA Mtb is retained in alveolar macrophages, impaired in recruiting and disseminating into monocyte-derived cells, and more likely to be localized in airway cells than wild-type Mtb. The lungs of ΔcpsA-infected mice also have markedly fewer antigen-specific T cells, indicating a delay in adaptive immunity. Thus, we conclude that CpsA promotes dissemination of Mtb from alveolar macrophages and the airways and generation of an adaptive immune response. Our studies of ΔcpsA Mtb show that a more effective innate immune response against Mtb can be undermined by a corresponding delay in the adaptive immune response.

Extended long-term follow-up of metastatic melanoma patients treated with immunotherapy: late relapses and second primary melanomas.

Background: Immunotherapy has revolutionized the treatment of patients with advanced melanoma as well as other cancers. Most studies, whether of interleukin-2 or checkpoint inhibitor therapies, have limited follow-up after 5 years, making the incidence of late relapses uncertain. In addition, the incidence of second primary melanomas in patients with stage IV melanoma treated with immunotherapy has rarely been reported. Methods: We performed a single-institution retrospective study of stage IV melanoma patients treated with interleukin-2 or checkpoint inhibitors over the period from 1992 to 2013. We found 59 patients alive and in remission 5 years after the beginning of immunotherapy and reviewed their subsequent clinical course. Results: This 59-patient cohort had a median follow-up of 13.1 years, with 36 patients followed up for at least 10 years. Four patients (6.8%) had relapses of their metastatic melanoma at 5, 8, 15, and 17 years after starting the successful immunotherapy. Three of the four are still alive. Only one patient in 690 patient-years of observation had a second primary invasive melanoma. Conclusion: Although late relapses after immunotherapy for melanoma do occur, we can conclude that the prognosis of stage IV melanoma patients in continuous remission 5 years after starting immunotherapy is excellent, with a progression-free survival of approximately 85% and a melanoma-specific survival of approximately 95% at 20 years in our series. Our incidence of second primary melanomas is lower than usually reported. These results have important implications regarding the follow-up of stage IV melanoma patients successfully treated with immunotherapy.

Microrchidia 2/histone deacetylase 1 complex regulates E-cadherin gene expression and function.

Although Microrchidia 2 (MORC2) is widely overexpressed in human malignancies and linked to cancer cell proliferation, metabolism, and metastasis, the mechanism of action of MORC2 in cancer cell migration and invasion is yet undeciphered. Here, we identified for the first time that MORC2, a chromatin remodeler, regulates E-cadherin expression and, subsequently regulates breast cancer cell migration and invasion. We observed a negative correlation between the expression levels of MORC2 and E-cadherin in breast cancer. Furthermore, the overexpression of MORC2 resulted in decreased expression levels of E-cadherin. In addition, co-immunoprecipitation and chromatin immunoprecipitation assays revealed that MORC2 interacts with HDAC1 and gets recruited onto the E-cadherin promoter to inhibit its transcription, thereby suppress its expression. Consequently, knockdown of HDAC1 in MORC2-overexpressing cells led to reduced cancer cell migration and invasion. Interestingly, we noticed that MORC2-regulated glucose metabolism via c-Myc, and LDHA, also modulates the expression of E-cadherin. Collectively, these results demonstrate for the first time a mechanistic role for MORC2 as an upstream regulator of E-cadherin expression and its associated functions in breast cancer.

Range selective phase-shifting frequency-modulated digital holography with temporal-heterodyning.

We demonstrate that a time of flight (TOF) camera can be used to perform range selective temporal-heterodyne frequency-modulated continuous wave digital holography (TH FMCW DH). The modulated arrayed detection of a TOF camera allows efficient integration of holograms at a selected range with range resolutions significantly less than the optical system's depth of field. TH FMCW DH also allows for on-axis geometries to be achieved, where background light not at the internal modulation frequency of the camera is filtered out. Range selective TH FMCW DH imaging was achieved for both image holograms and Fresnel holograms using on-axis DH geometries. A 2.39 GHz FMCW chirp bandwidth resulted in a DH range resolution of 6.3 cm.

Exploring the Boundaries of Reality: Investigating the Phenomenon of Artificial Intelligence Hallucination in Scientific Writing Through ChatGPT References.

Background Chatbots are computer programs that use artificial intelligence (AI) and natural language processing (NLP) to simulate conversations with humans. One such chatbot is ChatGPT, which uses the third-generation generative pre-trained transformer (GPT-3) developed by OpenAI. ChatGPT has been praised for its ability to generate text, but concerns have been raised about its accuracy and precision in generating data, as well as legal issues related to references. This study aims to investigate the frequency of AI hallucination in research proposals entirely drafted by ChatGPT. Methodology An analytical design was employed to investigate AI hallucination by ChatGPT. A total of 178 references listed by ChatGPT were verified for inclusion in the study. Statistical analysis was performed by five researchers who entered their data into a Google Form, and the final results were represented using pie charts and tables. Results Out of the 178 references analyzed, 69 references did not have a Digital Object Identifier (DOI), and 28 references neither turned up on Google search nor had an existing DOI. Three references were listed from books and not research articles. These observations suggest that ChatGPT's ability to generate reliable references for research topics may be limited by the availability of DOI and the accessibility of online articles. Conclusions The study highlights the potential limitations of ChatGPT's ability to generate reliable references for research proposals. AI hallucination is a problem that may negatively impact decision-making and may give rise to ethical and legal problems. Improving the training inputs by including diverse, accurate, and contextually relevant data sets along with frequent updates to the training models could potentially help address these issues. However, until these issues are addressed, researchers using ChatGPT should exercise caution in relying solely on the references generated by the AI chatbot.

Biodegradable Green Composites: Effects of Potassium Permanganate (KMnO4) Treatment on Thermal, Mechanical, and Morphological Behavior of Butea Parviflora (BP) Fibers.

This study emphasizes the importance of utilizing biodegradable material Butea parviflora (BP) fiber for sustainable solutions. BP fiber offers numerous ecological benefits, such as being lightweight, biodegradable, and affordable to recycle. The study examines the effects of potassium permanganate (KMnO4) treatment on BP fiber and analyzes its physical and chemical behavior using various methods, including X-ray Diffraction (XRD) analysis, tensile testing, thermogravimetric analysis, thermal conductivity, Scanning Electron Microscopy (SEM), and Fourier Transform Infrared spectroscopic (FTIR) analysis. The results demonstrate that BP fiber possesses low density (1.40 g/cc) and high cellulose content (59.4%), which fosters compatibility between the matrix and resin. XRD analysis indicates a high crystallinity index (83.47%) and crystallite size (6.4 nm), showcasing exceptional crystalline behavior. Treated fibers exhibit improved tensile strength (198 MPa) and Young's modulus (4.40 GPa) compared to untreated fibers (tensile strength-92 MPa, tensile modulus-2.16 GPa). The Tg-DTA thermograms reveal the fiber's thermal resistance up to 240 °C with a kinetic activation energy between 62.80-63.46 KJ/mol. Additionally, the lowered thermal conductivity (K) from Lee's disc experiment suggests that BP fiber could be used in insulation applications. SEM photographic results display effective surface roughness for composite making, and FTIR studies reveal vibrational variations of cellulosic functional groups, which correlates with increased cellulosic behavior. Overall, the study affirms the potential of BP fiber as a reinforcing material for composite-making while emphasizing the importance of utilizing biodegradable materials for sustainability.

Investigation on Properties of Raw and Alkali Treated Novel Cellulosic Root Fibres of Zea Mays for Polymeric Composites.

Today, new materials based on natural fibres have been emerging day by day to completely eradicate plastics to favour our environmental nature. In this view, the present work is based on the extraction and characterisation of the novel root fibres of the Zea mays (Zm) plant, grown by the hydroponic method. Both the dried untreated and alkali treated root fibres are investigated using a variety of structural, morphological, thermal, elemental and mechanical tests by subjecting both the samples to p-XRD, FT-IR, SEM-EDAX, TGA-DTA, CHNS and tensile strength analyses. Thermal conductivity of the untreated and treated fibres is found using Lee's disc experiment. From p-XRD analysis, the Crystallinity Index, Percentage Crystallinity and Crystallite size of the samples are found. FT-IR studies clarify the different vibrational groups associated with the fibre samples. SEM images show that the surface roughness increases for the chemically treated samples, such that it may be effectively utilised as reinforcement for polymeric composites. The diameter of the fibre samples is found using SEM analysis. According to the EDAX spectrum, Zm fibres in both their raw and processed forms have high levels of Carbon (C) and Oxygen (O). The TGA-DTA tests revealed that the samples of natural fibre have good thermal characteristics. CHNS studies show that Carbon content is high for these samples, which is the characteristic of many natural fibres. Chemical analysis is used to ascertain the prepared samples' chemical makeup. It reveals that both samples have significant amounts of cellulose. The density of the fibres is found to be in the range 0.3-0.6 g/cc, which is much less than any other natural fibre. Therefore, it can be used in light weight applications. From the tensile strength analysis, physical properties such as Young's modulus and micro-fibril angle are determined. The fibres in the roots exhibit a lower tensile strength. Thus, these fibres can be used in powdered form as reinforcement for natural rubber or epoxy composites. After examining all of its properties, it could be reasonably speculated that Zea mays root fibres can be considered as an efficient reinforcement for various matrices to produce attractive bio-composites.

Adaptive Sentinel Testing in Workplace for COVID-19 Pandemic.

Testing and isolation of infectious employees is one of the critical strategies to make the workplace safe during the pandemic for many organizations. Adaptive testing frequency reduces cost while keeping the pandemic under control at the workplace. However, most models aimed at estimating test frequencies were structured for municipalities or large organizations such as university campuses of highly mobile individuals. By contrast, the workplace exhibits distinct characteristics: employee positivity rate may be different from the local community because of rigorous protective measures at workplace, or self-selection of co-workers with common behavioral tendencies for adherence to pandemic mitigation guidelines. Moreover, dual exposure to COVID-19 occurs at work and home that complicates transmission modeling, as does transmission tracing at the workplace. Hence, we developed bi-modal SEIR (Susceptible, Exposed, Infectious, and Removed) model and R-shiny tool that accounts for these differentiating factors to adaptively estimate the testing frequency for workplace. Our tool uses easily measurable parameters: community incidence rate, risks of acquiring infection from community and workplace, workforce size, and sensitivity of testing. Our model is best suited for moderate-sized organizations with low internal transmission rates, no-outward facing employees whose position demands frequent in-person interactions with the public, and low to medium population positivity rates. Simulations revealed that employee behavior in adherence to protective measures at work and in their community, and the onsite workforce size have large effects on testing frequency. Reducing workplace transmission rate through workplace mitigation protocols and higher sensitivity of the test deployed, although to a lesser extent. Furthermore, our simulations showed that sentinel testing leads to only marginal increase in the number of infections even for high community incidence rates, suggesting that this may be a cost-effective approach in future pandemics. We used our model to accurately guide testing regimen for three campuses of the Jackson Laboratory.

NetAct: a computational platform to construct core transcription factor regulatory networks using gene activity.

A major question in systems biology is how to identify the core gene regulatory circuit that governs the decision-making of a biological process. Here, we develop a computational platform, named NetAct, for constructing core transcription factor regulatory networks using both transcriptomics data and literature-based transcription factor-target databases. NetAct robustly infers regulators' activity using target expression, constructs networks based on transcriptional activity, and integrates mathematical modeling for validation. Our in silico benchmark test shows that NetAct outperforms existing algorithms in inferring transcriptional activity and gene networks. We illustrate the application of NetAct to model networks driving TGF-ß-induced epithelial-mesenchymal transition and macrophage polarization.

A Genomically and Clinically Annotated Patient-Derived Xenograft Resource for Preclinical Research in Non-Small Cell Lung Cancer.

Patient-derived xenograft (PDX) models are an effective preclinical in vivo platform for testing the efficacy of novel drugs and drug combinations for cancer therapeutics. Here we describe a repository of 79 genomically and clinically annotated lung cancer PDXs available from The Jackson Laboratory that have been extensively characterized for histopathologic features, mutational profiles, gene expression, and copy-number aberrations. Most of the PDXs are models of non-small cell lung cancer (NSCLC), including 37 lung adenocarcinoma (LUAD) and 33 lung squamous cell carcinoma (LUSC) models. Other lung cancer models in the repository include four small cell carcinomas, two large cell neuroendocrine carcinomas, two adenosquamous carcinomas, and one pleomorphic carcinoma. Models with both de novo and acquired resistance to targeted therapies with tyrosine kinase inhibitors are available in the collection. The genomic profiles of the LUAD and LUSC PDX models are consistent with those observed in patient tumors from The Cancer Genome Atlas and previously characterized gene expression-based molecular subtypes. Clinically relevant mutations identified in the original patient tumors were confirmed in engrafted PDX tumors. Treatment studies performed in a subset of the models recapitulated the responses expected on the basis of the observed genomic profiles. These models therefore serve as a valuable preclinical platform for translational cancer research. SIGNIFICANCE: Patient-derived xenografts of lung cancer retain key features observed in the originating patient tumors and show expected responses to treatment with standard-of-care agents, providing experimentally tractable and reproducible models for preclinical investigations.

Adaptive sentinel testing in workplace for COVID-19 pandemic

Testing and isolation of infectious employees is one of the critical strategies to make the workplace safe during the pandemic for many organizations. Adaptive testing frequency reduces cost while keeping the pandemic under control at the workplace. However, most models aimed at estimating test frequencies were structured for municipalities or large organizations such as university campuses of highly mobile individuals. By contrast, the workplace exhibits distinct characteristics: employee positivity rate may be different from the local community because of rigorous protective measures at workplace, or self-selection of co-workers with common behavioral tendencies for adherence to pandemic mitigation guidelines. Moreover, dual exposure to COVID19 occurs at work and home that complicates transmission modelling, as does transmission tracing at the workplace. Hence, we developed bi-modal SEIR model and R-shiny tool that accounts for these differentiating factors to adaptively estimate the testing frequency for workplace. Our tool uses easily measurable parameters: community incidence rate, risks of acquiring infection from community and work-place, workforce size, and sensitivity of testing. Our model is best suited for moderate-sized organizations with low internal transmission rates, no-outward facing employees whose position demands frequent in-person interactions with the public, and low to medium population positivity rates. Simulations revealed that employee behavior in adherence to protective measures at work and in their community, and the onsite workforce size have large effects on testing frequency. Reducing workplace transmission rate through workplace mitigation protocols and higher sensitivity of the test deployed, though to a lesser extent. Furthermore, our simulations showed that sentinel testing leads to only marginal increase in the number of infections even for high community incidence rates, suggesting that this may be a cost-effective approach in future pandemics. We used our model to accurately guide testing regimen for three campuses of The Jackson Laboratory.

The All India Ophthalmological Society - Academic and Research Committee pan-India diabetic retinopathy project "Fixing the missing link": Prevalence data from Madhya Pradesh and Chhattisgarh.

Purpose: : To determine the prevalence of diabetic retinopathy (DR) and its risk factors among diabetic patients in the states of Madhya Pradesh (MP) and Chhattisgarh (CG). Methods: : Diabetic patients were screened in the treating diabetologist/physician's clinic by a team that included an ophthalmologist, an optometrist, and a counselor. Demographic details, diabetic control, compliance to eye checkup, awareness regarding diabetic blindness, and visual acuity were recorded using a questionnaire. DR was graded both by indirect ophthalmoscopy and fundus photo taken with a portable fundus camera. Results: : In total, 602 subjects were screened across five selected locations of MP and CG. The prevalence of DR was 13.62%. No significant difference with gender was seen. The presence and grade of DR were related to age, diabetic age, and diabetic control. Conclusion: : This study provides the prevalence data for DR among diabetic patients from the states of MP and CG and highlights important barriers to DR screening in our country.