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PURPOSEConstitutional mismatch repair deficiency (CMMRD) is a genetic cancer predisposition syndrome among children and young adults. This study aimed to evaluate the frequency of CMMRD among patients with pediatric high-grade glioma (pHGG) in a single tertiary care center in Pakistan, a country with high consanguinity rates.PATIENTS AND METHODSWe reviewed the data of patients age

Information theft and cyberbullying pose significant threats to users’ privacy on social media. This study applies Protection Motivation Theory (PMT) to explore how online information disclosure awareness and privacy concerns influence protective actions, such as regulated social media usage and detoxification, in response to negative experiences like data heist and cyberbullying. Analyzing survey responses from 1,000 social media users in Pakistan, ranging in age from 18 years to over 50, and using the snowball sampling technique, our findings reveal that awareness of online information disclosure mediates the relationship between data theft and regulated social media use. Privacy concerns similarly mediate the relationship between cyberbullying experiences and social media detoxification, aligning with PMT. In addition, negative online experiences directly correlate with privacy safety behaviors, indicating that motivations may not always drive protective actions. This research sheds light on the intricate dynamics between privacy concerns, negative online experiences, and protective behaviors, offering insights for interventions and policies to enhance users’ digital privacy and safety. Understanding these relationships is crucial for addressing the challenges of information theft and cyberbullying in the digital landscape.

During the Coronavirus disease of 2019 (COVID-19), the dissemination of false information on social media increased significantly. The examination of social factors influencing the proliferation of fake news related to COVID-19 necessitates exploration from various perspectives and dimensions. Our research surveyed 392 Pakistani social media consumers, employing a survey questionnaire method conducted through snowball sampling technique. We utilized SPSS 26.0 for descriptive statistics, Pearson correlation, and regression analysis. The mediation and moderation effects were tested using Andrew F. Hayes' Process program (V3.3). Our findings revealed that COVID-19-related fake news tends to spread through instant news sharing behavior, driven by socialization and entertainment motives, acting as mediating factors in the relationship between instant news sharing and the dissemination of false information. Altruism also plays a moderating role, playing a moderating role in the impact of instant news sharing on fake news sharing, and also playing a moderating role in the impact of socialization on fake news sharing. Employing a rational choice theory framework, our study identifies instant news sharing, socialization, entertainment, and altruism as key rational choices influencing the sharing of pandemic-related fake news among Pakistani social media users.

Background: Wilms Tumor (WT) is a highly curable cancer if treatment is appropriate and timely. The outcomes and prognostic factors in a large low- and middle-income country (LMIC) tertiary center were assessed. Materials and methods: Retrospective review of data of all patients, 0–15 years diagnosed between 2010 and 2020 with WT. Kaplan Meier curves were used for survival analysis, and the chi-square test was used for multivariate analysis. Results: Of the 40 patients enrolled (median age: 38 months) in the cohort, 10 had metastatic disease. The most common site of metastasis was lungs (6/10). Nine (22.5%) abandoned treatment. Large tumor (>500 ml) volume was found in half the patients at diagnosis. The majority of patients were treated per the SIOP approach. Out of 34 who went for surgery, 31 received neoadjuvant chemotherapy with tumor shrinkage to less than 500 ml in 26/31 (80%). Maximum tumor shrinkage was observed in the SIOP low-risk group (p

Background and purposeWe proposed an artificial neural network model to predict radiobiological parameters for the head and neck squamous cell carcinoma patients treated with radiation therapy. The model uses the tumor specification, demographics, and radiation dose distribution to predict the tumor control probability and the normal tissue complications probability. These indices are crucial for the assessment and clinical management of cancer patients during treatment planning.MethodsTwo publicly available datasets of 31 and 215 head and neck squamous cell carcinoma patients treated with conformal radiation therapy were selected. The demographics, tumor specifications, and radiation therapy treatment parameters were extracted from the datasets used as inputs for the training of perceptron. Radiobiological indices are calculated by open-source software using dosevolume histograms from radiation therapy treatment plans. Those indices were used as output in the training of a single-layer neural network. The distribution of data used for training, validation, and testing purposes was 70, 15, and 15%, respectively.ResultsThe best performance of the neural network was noted at epoch number 32 with the mean squared error of 0.0465. The accuracy of the prediction of radiobiological indices by the artificial neural network in training, validation, and test phases were determined to be 0.89, 0.87, and 0.82, respectively. We also found that the percentage volume of parotid inside the planning target volume is the significant parameter for the prediction of normal tissue complications probability.ConclusionWe believe that the model has significant potential to predict radiobiological indices and help clinicians in treatment plan evaluation and treatment management of head and neck squamous cell carcinoma patients.

IntroductionInitiated in June 2019, this collaborative effort involved 15 public and private sector hospitals in Pakistan. The primary objective was to enhance the capacity for pediatric neuro-oncology (PNO) care, supported by a My Child Matters/Foundation S grant.MethodsWe aimed to establish and operate Multidisciplinary Tumor Boards (MTBs) on a national scale, covering 76% of the population (185.7 million people). In response to the COVID-19 pandemic, MTBs transitioned to videoconferencing. Fifteen hospitals with essential infrastructure participated, holding monthly sessions addressing diagnostic and treatment challenges. Patient cases were anonymized for confidentiality. Educational initiatives, originally planned as in-person events, shifted to a virtual format, enabling continued implementation and collaboration despite pandemic constraints.ResultsA total of 124 meetings were conducted, addressing 545 cases. To augment knowledge, awareness, and expertise, over 40 longitudinal lectures were organized for healthcare professionals engaged in PNO care. Additionally, two symposia with international collaborators and keynote speakers were also held to raise national awareness. The project achieved significant milestones, including the development of standardized national treatment protocols for low-grade glioma, medulloblastoma, and high-grade glioma. Further protocols are currently under development. Notably, Pakistan's first pediatric neuro-oncology fellowship program was launched, producing two graduates and increasing the number of trained pediatric neuro-oncologists in the country to three.DiscussionThe initiative exemplifies the potential for capacity building in PNO within low-middle income countries. Success is attributed to intra-national twinning programs, emphasizing collaborative efforts. Efforts are underway to establish a national case registry for PNO, ensuring a comprehensive and organized approach to monitoring and managing cases. This collaborative initiative, supported by the My Child Matters/Foundation S grant, showcases the success of capacity building in pediatric neuro-oncology in low-middle income countries. The establishment of treatment protocols, fellowship programs, and regional tumor boards highlights the potential for sustainable improvements in PNO care.

Summary: Upon activation, vinculin reinforces cytoskeletal anchorage during cell adhesion. Activating ligands classically disrupt intramolecular interactions between the vinculin head and tail domains that bind to actin filaments. Here, we show that Shigella IpaA triggers major allosteric changes in the head domain, leading to vinculin homo-oligomerization. Through the cooperative binding of its three vinculin-binding sites (VBSs), IpaA induces a striking reorientation of the D1 and D2 head subdomains associated with vinculin oligomerization. IpaA thus acts as a catalyst producing vinculin clusters that bundle actin at a distance from the activation site and trigger the formation of highly stable adhesions resisting the action of actin relaxing drugs. Unlike canonical activation, vinculin homo-oligomers induced by IpaA appear to keep a persistent imprint of the activated state in addition to their bundling activity, accounting for stable cell adhesion independent of force transduction and relevant to bacterial invasion.

We report a case of a middle age male who presented to our tertiary care university hospital with the complaints of nasal obstruction and decrease hearing. The CT scan of head and neck exhibited a mass in nasopharynx and enlarged bilateral cervical lymph nodes. Biopsy from nasopharynx confirmed the lesion as poorly differentiated non-keratinizing squamous cell carcinoma and staged as cT2N2M0. He received neoadjuvant chemotherapy. Subsequently, he underwent chemo radiation therapy. He represented with left chest wall pain. Imaging confirmed isolated lesion on left sided 6th rib. Rib lesion was resected followed by radiation therapy to surgical bed and systemic treatment. The patient remained disease free for 4.5 years. Later, his disease relapsed, and he died of systemic disease progression. --Continue

In Aga Khan University, a retrospective review was conducted from January 2013-December 2020 for patients who received Total Skin Electron Beam Therapy (TSEBT) for the management of Mycosis Fungoides (MF). The clinical response rate and disease-free interval (DFI) was evaluated for three patients. All of the patients received a 3600 cGy dose of radiation. Clinical complete remission (cCR) was observed in two out of three patients, while one patient showed clinical partial response. Following the cCR to TSEBT, the DFI of the first patient with stage 1B lasted 30 months, while the second patient with stage IIB remained disease free for five months. TSEBT is an effective treatment for MF disease. It can thus be expected that patients with limited disease in the early stage can acquire a cCR with a longer DFI. ---Continue

OBJECTIVE: To report laryngeal movement during simulation for radiation treatment planning in patients with laryngeal carcinoma. METHODS AND MATERIALS: A retrospective review of patients diagnosed with laryngeal carcinoma treated with radiation therapy was done. Movement of the larynx in cephalo-caudal direction was noted with help of fluoroscopic images taken during resting and deglutition phases. Information of variables such as patients age, gender, tracheostomy status, stage of disease and sub-site of disease were recorded. Simple linear regression was used to assess the linear relationship between laryngeal movement and different variables. RESULTS: A total of 47 patients were identified between February 2006 and December 2017 whose laryngeal movement was documented during simulation. About half of the patients had stage I disease (n = 22 [46.8%]). In majority of the patients, the disease originated in glottis (n = 37 [78.7%]). The mean laryngeal movement was noted to be 0.96 cm (SD of 0.392, range: 0.5-2.0cm). There was no linear association observed between laryngeal movement and age (p = 0.239), gender (p = 0.369), tracheostomy status (p = 0.664), stage of disease (p = 0.322) or sub-site of disease (p = 0.761). CONCLUSION: In this era of precision, recording laryngeal movement and incorporating in contouring remains important because it can lead to geometrical miss of target volume during radiation delivery. Our study shows a physiological motion of nearly 1 cm in a cephalo-caudal direction. We conclude that a cautious margin of planning target volume (PTV) should be considered and incorporated during radiation planning of laryngeal cancers. [ABSTRACT FROM AUTHOR]

Kidney injury is a known late and potentially devastating complication of abdominal radiation therapy (RT) in pediatric patients. A comprehensive Pediatric Normal Tissue Effects in the Clinic review by the Genitourinary (GU) Task Force aimed to describe RT dose-volume relationships for GU dysfunction, including kidney, bladder, and hypertension, for pediatric malignancies. The effect of chemotherapy was also considered. We conducted a comprehensive PubMed search of peer-reviewed manuscripts published from 1990 to 2017 for investigations on RT-associated GU toxicities in children treated for cancer. We retrieved 3271 articles with 100 fulfilling criteria for full review, 24 with RT dose data and 13 adequate for modeling. Endpoints were heterogenous and grouped according to National Kidney Foundation: grade ≥1, grade ≥2, and grade ≥3. We modeled whole kidney exposure from total body irradiation (TBI) for hematopoietic stem cell transplant and whole abdominal irradiation (WAI) for patients with Wilms tumor. Partial kidney tolerance was modeled from a single publication from 2021 after the comprehensive review revealed no usable partial kidney data. Inadequate data existed for analysis of bladder RT-associated toxicities. The 13 reports with long-term GU outcomes suitable for modeling included 4 on WAI for Wilms tumor, 8 on TBI, and 1 for partial renal RT exposure. These reports evaluated a total of 1191 pediatric patients, including: WAI 86, TBI 666, and 439 partial kidney. The age range at the time of RT was 1 month to 18 years with medians of 2 to 11 years in the various reports. In our whole kidney analysis we were unable to include chemotherapy because of the heterogeneity of regimens and paucity of data. Age-specific toxicity data were also unavailable. Wilms studies occurred from 1968 to 2011 with mean follow-ups 8 to 15 years. TBI studies occurred from 1969 to 2004 with mean follow-ups of 4 months to 16 years. We modeled risk of dysfunction by RT dose and grade of toxicity. Normal tissue complication rates ≥5%, expressed as equivalent doses, 2 Gy/fx for whole kidney exposures occurred at 8.5, 10.2, and 14.5 Gy for National Kidney Foundation grades ≥1, ≥2, and ≥3, respectively. Conventional Wilms WAI of 10.5 Gy in 6 fx had risks of ≥grade 2 toxicity 4% and ≥grade 3 toxicity 1%. For fractionated 12 Gy TBI, those risks were 8% and <3%, respectively. Data did not support whole kidney modeling with chemotherapy. Partial kidney modeling from 439 survivors who received RT (median age, 7.3 years) demonstrated 5 or 10 Gy to 100% kidney gave a <5% risk of grades 3 to 5 toxicity with 1500 mg/m2 carboplatin or no chemo. With 480 mg/m2 cisplatin, a 3% risk of ≥grade 3 toxicity occurred without RT and a 5% risk when 26% kidney received ≥10 Gy. With 63 g/m2 of ifosfamide, a 5% risk of ≥grade 3 toxicity occurred with no RT, and a 10% toxicity risk occurred when 42% kidney received ≥10 Gy. In patients with Wilms tumor, the risk of toxicity from 10.5 Gy of WAI is low. For 12 Gy fractionated TBI with various mixtures of chemotherapy, the risk of severe toxicity is low, but low-grade toxicity is not uncommon. Partial kidney data are limited and toxicity is associated heavily with the use of nephrotoxic chemotherapeutic agents. Our efforts demonstrate the need for improved data gathering, systematic follow-up, and reporting in future clinical studies. Current radiation dose used for Wilms tumor and TBI appear to be safe; however, efforts in effective kidney-sparing TBI and WAI regimens may reduce the risks of renal injury without compromising cure. [ABSTRACT FROM AUTHOR]