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Lynch syndrome predisposes to a high risk of colorectal cancer and colonoscopy remains the primary preventive strategy. The prevention of colorectal cancer through colonoscopy relies on identifying and removing adenomas, the main precursor lesion. Nevertheless, colonoscopy is not an optimal strategy since post-colonoscopy colorectal cancer remains an important issue. In continuation of a 2021 journal review, the present article seeks to offer an updated perspective by examining relevant articles from the past 3 years. We place recent findings in the context of existing guidelines, with a specific focus on colonoscopy surveillance. Key aspects explored include colonoscopy quality standards, timing of initiation, and surveillance intervals. Our review provides a comprehensive analysis of adenoma-related insights in Lynch syndrome, delving into emerging technologies like virtual chromoendoscopy and artificial intelligence-assisted endoscopy. This review aims to contribute valuable insights into the topic of colonoscopy surveillance in Lynch syndrome. [ABSTRACT FROM AUTHOR]

ABSTRACT The importance of state capacity and institutional quality has received significant attention within the academic literature. This is especially true as it relates to the protection of property rights and, ultimately, the role it plays in economic development. This study adds to this literature by considering how lynching activity across US states impacts sovereign credit. Given that lynching tends to be associated with weak public‐sector institutions, limited‐access social orders, and the weak protection of individual and property rights, we posit that as lynchings increase so too will bond yields. The analysis covers the period 1883–1920 and find support that state borrowing costs rose as lynching activity increased. The results are robust to a number of specifications, demographic groups, and regions. Implications are discussed. [ABSTRACT FROM AUTHOR]

Lynch's (1960) Theory of Imageability explores how individuals perceive and navigate urban environments, emphasizing the role of paths, edges, districts, nodes, and landmarks. This theory highlights the significance of these elements in shaping people's mental maps and enhancing their understanding and navigation of urban spaces. However, cultural tourism introduces complexities to Lynch's framework due to its unique motivations, interests, and behaviours. This article investigates the relationship between visitor mobility patterns and urban morphology in the context of two cultural destinations: Bilbao and San Sebastian. The study utilizes Network Analysis of visitors' GPS data to analyse the dynamics of visitor mobility within these urban environments. This data-driven approach facilitates a comprehensive understanding of how cultural destinations operate within their physical territories. Results reveal that both San Sebastian and Bilbao exhibit a distinct "D-shaped" mobility pattern, characterized by a clear and uncomplicated flow of movement. This finding aligns with Lynch's theory (1960), emphasizing the importance of simplicity and legibility in shaping visitors' cognitive maps and mental representations of the urban space. The concentration of cultural landmarks in the Old Town and the challenges of congestion and overtourism are brought to light through the network analysis of GPS data. The accompanying figures visually illustrate how the ease of navigation in these cities significantly contributes to the formation of visitors' cognitive maps. [ABSTRACT FROM AUTHOR]

Simple Summary: This study examined the efficacy and diagnostic yield of founder variant testing as an initial screening method for individuals with a personal or family history of cancer. The results indicate that this approach is ineffective and has a limited ability to detect significant germline variants. Given these findings, we raise doubts about the benefits of employing such testing and suggest a transition from a two-step approach to expansive genetic testing. Founder pathogenic variants (PVs) are prevalent in Israel. This study investigated the current practice of offering cancer patients two-step genetic testing, starting with targeted testing for recurring founder PVs, followed, if negative, by next-generation sequencing. A total of 2128 subjects with cancer or a positive family history underwent oncogenetic testing with a panel of 51 recurring PVs at a tertiary medical center in March 2020–January 2023. Those with a known familial PV (n = 370) were excluded from the analysis. Among the remainder, 128/1758 (7%) were heterozygous for at least one variant, and 44 (34%) carried a PV of medium-high penetrance (MHPV). Cancer was diagnosed in 1519/1758 patients (86%). The diagnostic yield of founder MHPV testing was 2% in cancer patients and 4% in healthy individuals with a positive family history. It was higher in Ashkenazi Jews than non-Ashkenazi Jews and Arabs, but not over 10% for any type of cancer, and it was significantly higher in younger (<40 years) than older (>50 years) individuals (7% vs. 1%). Eighty-four of the heterozygotes (66%), mostly Ashkenazi Jews, harbored a low-penetrance variant (LPV) not associated with the diagnosed cancer, usually APC c.3902T>A. These findings question the advantage of two-step testing. LPVs should not be included in targeted testing because this can lead to an overestimation of the yield, and their detection does not preclude further comprehensive testing. [ABSTRACT FROM AUTHOR]

Background: The DNA mismatch repair (MMR) system is a highly preserved protein complex recognizing short insertions, short deletions, and single base mismatches during DNA replication and recombination. MMR protein status is identified using immunohistochemistry. Deficit in one or more MMR proteins, configuring deficient MMR status (dMMR), leads to frameshift mutations particularly clustered in microsatellite repeats. Thus, microsatellite instability (MSI) is the epiphenomenon of dMMR. In colorectal cancer (CRC), MMR/MSI status is a biomarker with prognostic and predictive value of resistance to 5-fluorouracil and response to immune checkpoint inhibitor therapy. Summary: In this Review, we describe the challenges the practicing pathologist may face in relation to the assessment of MMR/MSI status and any open issues which still need to be addressed, focusing on pre-analytic issues, pitfalls in the interpretation, and technical aspects of the different assays. Key Messages: The current methods of detecting dMMR/MSI status have been optimized for CRCs, and whether these techniques can be applied to all tumor and specimen types is still not fully understood. Following the Food and Drug Administration (FDA), tissue/site agnostic drug approval of pembrolizumab for advanced/metastatic MSI tumors, MMR/MSI status in gastrointestinal tract is a common request from the oncologist. In this setting, several issues still need to be addressed, including criteria for sample adequacy. [ABSTRACT FROM AUTHOR]

Guidelines recommend risk-reducing bilateral salpingo-oophorectomy (RRSO) for women with pathogenic variants of non-BRCA and Lynch syndrome-associated ovarian cancer susceptibility genes. Optimal timing and findings at the time of RRSO for these women remains unclear. We sought to characterize practice patterns and frequency of occult gynecologic cancers for these women at our two institutions. Women with germline ovarian cancer susceptibility gene pathogenic variants who underwent RRSO between 1/2000–9/2019 were reviewed in an IRB-approved study. All patients were asymptomatic with no suspicion for malignancy at time of RRSO. Clinico-pathologic characteristics were extracted from the medical records. 26 Non-BRCA (9 BRIP1 , 9 RAD51C , and 8 RAD51D) and 75 Lynch (36 MLH1 , 18 MSH2 , 21 MSH6) pathogenic variants carriers were identified. Median age at time of RRSO was 47. There were no occurrences of occult ovarian or fallopian tube cancer in either group. Two patients (3%) in the Lynch group had occult endometrial cancer. Median follow up was 18 and 35 months for non-BRCA and Lynch patients, respectively. No patient developed primary peritoneal cancer upon follow up. Post-surgical complications occurred in 9/101 (9%) of patients. Hormone replacement therapy (HRT) was rarely used despite reported post-menopausal symptoms in 6/25 (23%) and 7/75 (37%) patients, respectively. No occult ovarian or tubal cancers were observed in either group. No recurrent or primary gynecologic-related cancers occurred upon follow-up. Despite frequent menopausal symptoms, HRT use was rare. Both groups experienced surgical complications when hysterectomy and/or concurrent colon surgery was performed suggesting concurrent surgeries should only be performed when indicated. • Median age of RRSO was 47 yo with no occult ovarian/fallopian tube cancer supporting current RRSO guidelines. • Surgical complications in this population were largely seen with concomitant hysterectomy and colectomy. • There was very low uptake in post-surgery hormone replacement therapy in these patients undergoing RRSO. [ABSTRACT FROM AUTHOR]

Objective: Lynch Syndrome (LS) carriers have a significantly increased risk of developing colorectal cancer (CRC) during their lifetimes. Further stratification of this patient population may help in identifying additional risk factors that predispose to colorectal carcinogenesis. In most LS patients CRC may arise from adenomas, although an alternative non-polypoid carcinogenesis pathway has been proposed for PMS2 carriers. Using data from our institutional LS cohort, our aim was to describe our current colorectal screening outcomes with a focus on the incidence of adenomas in the context of different MMR genotypes and patient demographics such as gender, race, and ethnicity. Design: We collected demographics, genetic, colonoscopy, and pathology results from a total of 163 LS carriers who obtained regular screening care at MD Anderson Cancer Center. Data were extracted from the electronic health records into a REDCap database for analysis. Logistic regressions were performed to measure the association between MMR variants and the likelihood of adenomas, advanced adenomas, and CRC. Then, we analyzed the cumulative incidences of these outcomes for the first 36 months following enrollment using Kaplan-Meier incidence curves, and Cox proportional hazard regressions. Results: On multivariate analysis, age (=45 years old) was associated with an increased risk of developing adenomas (P=0.034). Patients with a prior or active cancer status were less likely to develop adenomas (P=0.015), despite of the lack of association between surgical history with this outcome (P=0.868). We found no statistically significant difference in likelihood of adenoma development between MLH1 and MSH2/EPCAM, MSH6, and PMS2 carriers. Moreover, we observed no statistically significant difference in the likelihood of advanced adenomas or CRC for any measured covariates. On Cox proportional hazard, compared to MLH1 carriers, the incidence of adenomas was highest among MSH2/EPCAM carriers during for the first 36-months of follow-up (P<0.001). We observed a non-statistically significant trend for Hispanics having a higher and earlier cumulative incidence of adenomas compared to non-Hispanics (P=0.073). No MMR carrier was more likely to develop advanced adenomas. No difference in the incidence of CRC by MMR gene (P=0.198). Conclusion: Screening recommendations for CRC in LS patients should be based on specific MMR variants and should also be tailored to consider patient demographics. [ABSTRACT FROM AUTHOR]

BackgroundGermline genetic testing increasingly identifies advanced prostate cancer (PCa) patients who are candidates for precision therapies. The Prostate Cancer Clinical Trials Consortium (PCCTC) established the Germline Genetics Working Group to provide guidance and resources to expand effective use of germline genetic testing.Materials and methodsA 14-item questionnaire was e-mailed to academic oncologists at 43 PCCTC sites to collect information on germline genetic testing patterns, including patients considered, choice of assays, barriers slowing adoption, and actions to overcome barriers.ResultsTwenty-six genitourinary oncologists from 19 institutions responded. Less than 40% (10 of 26) reported referring patients to a genetics department, whereas the remainder take personal responsibility for genetic testing and counseling; 16 (62%) consider testing all metastatic PCa patients, whereas 3 (12%) consider testing all patients with high-risk local disease; and 7 (27%) use multigene comprehensive pan-cancer panels, and 14 (54%) use smaller or targeted cancer gene panels. Barriers to widespread use are: (1) delayed or limited access to genetic counseling; (2) no insurance coverage; (3) lack of effective workflows; (4) insufficient educational materials; and (5) time and space constraints in busy clinics. The primary limitation was the

ObjectiveLynch Syndrome (LS) carriers have a significantly increased risk of developing colorectal cancer (CRC) during their lifetimes. Further stratification of this patient population may help in identifying additional risk factors that predispose to colorectal carcinogenesis. In most LS patients CRC may arise from adenomas, although an alternative non-polypoid carcinogenesis pathway has been proposed for PMS2 carriers. Using data from our institutional LS cohort, our aim was to describe our current colorectal screening outcomes with a focus on the incidence of adenomas in the context of different MMR genotypes and patient demographics such as gender, race, and ethnicity.DesignWe collected demographics, genetic, colonoscopy, and pathology results from a total of 163 LS carriers who obtained regular screening care at MD Anderson Cancer Center. Data were extracted from the electronic health records into a REDCap database for analysis. Logistic regressions were performed to measure the association between MMR variants and the likelihood of adenomas, advanced adenomas, and CRC. Then, we analyzed the cumulative incidences of these outcomes for the first 36 months following enrollment using Kaplan-Meier incidence curves, and Cox proportional hazard regressions.ResultsOn multivariate analysis, age (≥45 years old) was associated with an increased risk of developing adenomas (P=0.034). Patients with a prior or active cancer status were less likely to develop adenomas (P=0.015), despite of the lack of association between surgical history with this outcome (P=0.868). We found no statistically significant difference in likelihood of adenoma development between MLH1 and MSH2/EPCAM, MSH6, and PMS2 carriers. Moreover, we observed no statistically significant difference in the likelihood of advanced adenomas or CRC for any measured covariates. On Cox proportional hazard, compared to MLH1 carriers, the incidence of adenomas was highest among MSH2/EPCAM carriers during for the first 36-months of follow-up (P

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Background: Lynch syndrome has not traditionally been considered to have a high colorectal adenoma burden. However, with increasing adenoma detection rates in the general population, the incidence of adenoma detection in Lynch syndrome may also be increasing and leading to higher cumulative adenoma counts. Aim: To clarify the prevalence and clinical impact of multiple colorectal adenomas (MCRA) in Lynch syndrome. Methods: A retrospective review of patients with Lynch syndrome at our institution was performed to assess for MCRA (defined as ≥10 cumulative adenomas). Results: There were 222 patients with Lynch syndrome among whom 14 (6.3%) met MCRA criteria. These patients had increased incidence of advanced neoplasia (OR 10, 95% CI: 2.7-66.7). Conclusions: MCRA is not unusual in Lynch syndrome and is associated with a significantly increased likelihood of advanced colon neoplasia. Consideration should be given to differentiating colonoscopy intervals based on the presence of polyposis in Lynch syndrome. [ABSTRACT FROM AUTHOR]

BackgroundLynch syndrome has not traditionally been considered to have a high colorectal adenoma burden. However, with increasing adenoma detection rates in the general population, the incidence of adenoma detection in Lynch syndrome may also be increasing and leading to higher cumulative adenoma counts.AimTo clarify the prevalence and clinical impact of multiple colorectal adenomas (MCRA) in Lynch syndrome.MethodsA retrospective review of patients with Lynch syndrome at our institution was performed to assess for MCRA (defined as ≥10 cumulative adenomas).ResultsThere were 222 patients with Lynch syndrome among whom 14 (6.3%) met MCRA criteria. These patients had increased incidence of advanced neoplasia (OR 10, 95% CI: 2.7-66.7).ConclusionsMCRA is not unusual in Lynch syndrome and is associated with a significantly increased likelihood of advanced colon neoplasia. Consideration should be given to differentiating colonoscopy intervals based on the presence of polyposis in Lynch syndrome.

This study examines whether a change in the criteria for genetic testing for ovarian cancer risk changed the nature of referrals into our Familial Cancer service. This is a retrospective review of 273 women who underwent risk reducing surgery (RRS). The primary outcome was to establish whether there was an increase in women having RRS with a confirmed genetic mutation. Secondary outcomes included the incidence of occult cancer and of subsequent primary peritoneal cancer. The results showed an increase in women being offered RRS based on genetic diagnosis; 91% versus 32% before the criteria change. Four occult malignancies (1.5%) and two peritoneal cancers (0.7%) were noted. We have demonstrated a change in the nature of referrals to the familial cancer service from perceived risk to genetic diagnosis. We can now counsel women more accurately. With a defined risk we are enabling them to make an informed decision regarding risk reduction. [ABSTRACT FROM AUTHOR]

Background: Lynch syndrome (LS) is one of the commonest genetic cancer syndromes, with an incidence rate of 1 per 250–1000 population. The aim of this study was to evaluate the frequency and characteristics of MMR deficiency in endometrial cancer in Iranian women. Methods: One hundred endometrial carcinoma cases who referred to the gynecological oncology clinic of Imam Hossein Medical Center located in Tehran, Iran, from 2018 to 2020 were included in the study. Immunohistochemistry (IHC) evaluation was performed mainly on the hysterectomy specimens of all endometrial cancer (EC) patients to assess MMR proteins (MLH1, MSH2, MSH6, and PMS2) expression. Results: A total of 23 out of 100 (23%) cases were identified through IHC screening to be MMR-deficient. The most common types were loss of MLH1/PMS2 (17.4%) and solitary MSH2 (17.4%) expressions followed by PMS2/MSH2 loss (13%). MMR deficiency (dMMR) histopathology was significantly overrepresented in patients with family history of cancer or Lynch syndrome (LS) associated cancers (p-values of 0.016 and 0.005, respectively). The rate of myometrial invasion and lower uterine segment involvement were also significantly higher in dMMR EC patients compared to MMR-intact EC (p-value of 0.021 and 0.018, respectively). Conclusion: MMR deficiency, observed in 23% of endometrial cancer cases, was associated with higher rates of poor prognostic factors including myometrial invasion and lower uterine segment involvement. The presence of positive family history of cancer and family history of LS-associated cancer increased the probability of MMR-deficiency in endometrioid endometrial cancer to 47% and 70%, respectively. [ABSTRACT FROM AUTHOR]

An independent judiciary is a centrally important economic institution, and one that facilitates and promotes the protection of property rights, thereby fostering economic growth and development. On the other hand, extrajudicial lynchings, at least in the context of US states, have been tied to a lack of property rights and their protection (Carden in Institutions and southern development: lynching as a signal of insecure property rights. Ph.D. Dissertation. Washington University, 2006). However, these two areas of research have not been simultaneously explored. This study rectifies that by evaluating how a relatively independent judiciary might affect lynching rates across US states between 1883 and 1930. Overall, the results suggest that a relatively more independent judiciary (as measured through the method of selection and term length) is associated with a lower likelihood of observing a lynching in a given jurisdiction. This is true for both state courts of last resort and state courts of general jurisdiction. [ABSTRACT FROM AUTHOR]

Lynch syndrome (LS) is a condition which predisposes individuals primarily to early-onset colorectal and endometrial cancer. LS is characterized by a germline pathogenic variant in one of the MMR (MisMatch Repair) gene, inducing a phenotype of microsatellite instability in the tumor, which may be associated with a loss of expression of MMR proteins detected by standard immunohistochemistry on tumor tissue. Most of the time, LS is inherited from a parent in whom the condition may not be known due to incomplete penetrance, but de novo pathogenic variant is a rare occurrence. Here, we describe the case of a 52-year-old woman with no family history of LS, referred to the genetics department for colorectal cancer at the age of 50. Genetic analysis revealed a de novo germline pathogenic variant in the MSH6 gene. To date, this case is only the second report of a de novo pathogenic variant in the MSH6 gene in Lynch syndrome. De novo mutations have been extensively studied over the past years, but little is known about their origin and mechanism of occurrence in MMR genes. However, knowledge of mutation status allows better cancer risk management for the patient and an appropriate genetic testing and counseling for her family. [ABSTRACT FROM AUTHOR]

Window views can enable restorativeness. Previous studies define characteristics of natural environment that trigger restorativeness, but fewer studies are dealing with restorative characteristics of urban environment. The purpose of this study is to identify qualities that enable restorativeness in natural and urban window views. Using a questionnaire survey as a method for obtaining the research data, responses of architectural students are analysed. To identify restorative potential in window views evaluation method according to Kaplan's Attention Restoration Theory (ART) is used. Additional evaluation method for urban views is applied using Lynch's theory of designing urban space that people can enjoy. Our findings show that urban views can be analysed according to Lynch's visual qualities to identify the restorative potential of urban environments. Our findings also show that Lynch's criteria may coincide with Kaplan's criteria for assessing restorativeness. To define restorative potential in urban views in an early design phase, new evaluation methods are needed to transcend the renowned Kaplan's Attention Restoration Theory into more approachable design mechanisms for designers and decision makers. Well-being of the inhabitants in a future dense urban environment will only be provided with an adequate window view. [ABSTRACT FROM AUTHOR]

The clinical value of population-based genetic screening projects depends on the actions taken on the findings. The Healthy Nevada Project (HNP) is an all-comer genetic screening and research project based in northern Nevada. HNP participants with CDC Tier 1 findings of hereditary breast and ovarian cancer syndrome (HBOC), Lynch syndrome (LS), or familial hypercholesterolemia (FH) are notified and provided with genetic counseling. However, the HNP subsequently takes a "hands-off" approach: it is the responsibility of notified participants to share their findings with their healthcare providers, and providers are expected to implement the recommended action plans. Thus, the HNP presents an opportunity to evaluate the efficiency of participant and provider responses to notification of important genetic findings, using electronic health records (EHRs) at Renown Health (a large regional hospital in northern Nevada). Out of 520 HNP participants with findings, we identified 250 participants who were notified of their findings and who had an EHR. 107 of these participants responded to a survey, with 76 (71%) indicating that they had shared their findings with their healthcare providers. However, a sufficiently specific genetic diagnosis appeared in the EHRs and problem lists of only 22 and 10%, respectively, of participants without prior knowledge. Furthermore, review of participant EHRs provided evidence of possible relevant changes in clinical care for only a handful of participants. Up to 19% of participants would have benefited from earlier screening due to prior presentation of their condition. These results suggest that continuous support for both participants and their providers is necessary to maximize the benefit of population-based genetic screening. We recommend that genetic screening projects require participants' consent to directly document their genetic findings in their EHRs. Additionally, we recommend that they provide healthcare providers with ongoing training regarding documentation of findings and with clinical decision support regarding subsequent care. [ABSTRACT FROM AUTHOR]

Polymerase proofreading‐associated polyposis (PPAP) and Lynch syndrome, caused by mutated POLE and mismatch repair (MMR) genes, respectively, are associated with adult‐onset cancer. PPAP and MMR‐deficient tumors are both hypermutated, and each has a unique mutational signature. We describe a 4.5‐year‐old boy with multiple café au lait spots who presented with metastatic Sonic Hedgehog‐activated medulloblastoma, with partial response to intensive chemotherapy and immunotherapy. The tumor showed microsatellite stability, loss of PMS2 nuclear expression, and an exceptionally high tumor mutational burden of 276 Mut/Mb. Germline molecular analysis revealed an inherited heterozygous pathogenic POLE variant and a de novo heterozygous PMS2 pathogenic variant. The tumor featured the MMR, POLE, and POLE+MMR mutational signatures. This is the first description of a di‐genic condition, which we named "POL‐LYNCH syndrome," manifested by an aggressive ultra‐mutant pediatric medulloblastoma with a unique genomic signature. [ABSTRACT FROM AUTHOR]

The clinical value of population-based genetic screening projects depends on the actions taken on the findings. The Healthy Nevada Project (HNP) is an all-comer genetic screening and research project based in northern Nevada. HNP participants with CDC Tier 1 findings of hereditary breast and ovarian cancer syndrome (HBOC), Lynch syndrome (LS), or familial hypercholesterolemia (FH) are notified and provided with genetic counseling. However, the HNP subsequently takes a “hands-off” approach: it is the responsibility of notified participants to share their findings with their healthcare providers, and providers are expected to implement the recommended action plans. Thus, the HNP presents an opportunity to evaluate the efficiency of participant and provider responses to notification of important genetic findings, using electronic health records (EHRs) at Renown Health (a large regional hospital in northern Nevada). Out of 520 HNP participants with findings, we identified 250 participants who were notified of their findings and who had an EHR. 107 of these participants responded to a survey, with 76 (71%) indicating that they had shared their findings with their healthcare providers. However, a sufficiently specific genetic diagnosis appeared in the EHRs and problem lists of only 22 and 10%, respectively, of participants without prior knowledge. Furthermore, review of participant EHRs provided evidence of possible relevant changes in clinical care for only a handful of participants. Up to 19% of participants would have benefited from earlier screening due to prior presentation of their condition. These results suggest that continuous support for both participants and their providers is necessary to maximize the benefit of population-based genetic screening. We recommend that genetic screening projects require participants’ consent to directly document their genetic findings in their EHRs. Additionally, we recommend that they provide healthcare providers with ongoing training regarding documentation of findings and with clinical decision support regarding subsequent care.

Mob Lynching is an emerging trend as a new Crime in the shade of mob violence all over the country. Being a part of India, in Assam people belong to different cultural groups, linguistic groups, caste, community and religious groups use to live together with the feeling of unity, integrity and fraternity. In Assam like other parts of the country, 'Mob Lynch' is the term which becomes much familiar to the people of the region because every now and then it has been highlighted through the available Electronic Media of the State that some person(s) is/are being killed by a mob violence on suspicion of Child Lifter or Witch hunting etc.; Villagers lynched to death a women on suspect of that she is practicing Black Magic and a Witch; a Boy lynched to death in a place where he went to meet his relatives etc. many other such cases occurred which is nothing but a curse of the modern society. Assam has registered huge number of Mob Lynching cases every year in the state like Honour Killings, Witch Hunting, on suspicion of Child Lifters, on Communal riots, Pickpockets, Thefts etc. 'Mob' is an English term which means 'uncontrolled group of people' and 'Lynch' is an American term which means 'award of punishment to the wrong doers without any legal trial or proceedings'. According to the Data available of the Government of Assam during 2011-2019 shows that there were 107 persons killed in Witch Hunting incidents in the state. The present study aims to understand and explain what is Mob Lynching? What are the causes of lynching? What are the available legal provisions and laws to deal with such type of cases? What are the preventive and remedial measures that have been adopted by the state government and other Agencies and NGOs including the various Legal proceedings of the High Courts and the Hon'ble Supreme Court of India? [ABSTRACT FROM AUTHOR]

Diffuse IDH-mutant astrocytoma mostly occurs in adults and carries a favorable prognosis compared to IDH-wildtype malignant gliomas. Acquired mismatch repair deficiency is known to occur in recurrent IDH-mutant gliomas as resistance mechanism towards alkylating chemotherapy. In this multi-institutional study, we report a novel epigenetic group of 32 IDH-mutant gliomas with proven or suspected hereditary mismatch repair deficiency. None of the tumors exhibited a combined 1p/19q deletion. These primary mismatch repair-deficient IDH-mutant astrocytomas (PMMRDIA) were histologically high-grade and were mainly found in children, adolescents and young adults (median age 14 years). Mismatch repair deficiency syndromes (Lynch or Constitutional Mismatch Repair Deficiency Syndrom (CMMRD)) were clinically diagnosed and/or germline mutations in DNA mismatch repair genes (MLH1, MSH6, MSH2) were found in all cases, except one case with a family and personal history of colon cancer and another case with MSH6-deficiency available only as recurrent tumor. Loss of at least one of the mismatch repair proteins was detected via immunohistochemistry in all, but one case analyzed. Tumors displayed a hypermutant genotype and microsatellite instability was present in more than half of the sequenced cases. Integrated somatic mutational and chromosomal copy number analyses showed frequent inactivation of TP53, RB1 and activation of RTK/PI3K/AKT pathways. In contrast to the majority of IDH-mutant gliomas, more than 60% of the samples in our cohort presented with an unmethylated MGMT promoter. While the rate of immuno-histochemical ATRX loss was reduced, variants of unknown significance were more frequently detected possibly indicating a higher frequency of ATRX inactivation by protein malfunction. Compared to reference cohorts of other IDH-mutant gliomas, primary mismatch repair-deficient IDH-mutant astrocytomas have by far the worst clinical outcome with a median survival of only 15 months irrespective of histological or molecular features. The findings reveal a so far unknown entity of IDH-mutant astrocytoma with high prognostic relevance. Diagnosis can be established by aligning with the characteristic DNA methylation profile, by DNA-sequencing-based proof of mismatch repair deficiency or immunohistochemically demonstrating loss-of-mismatch repair proteins. [ABSTRACT FROM AUTHOR]

Background: The primary benefit of post-colorectal cancer (CRC) colonoscopic surveillance is to detect and remove premalignant lesions to prevent metachronous CRC. Current guidelines for long-term colonoscopic surveillance post early age onset CRC (EOCRC) resection are based on limited evidence. The aims of this study were to assess the diagnostic yield of colonoscopic surveillance post-EOCRC resection and identify molecular and clinicopathological risk factors associated with advanced neoplasia., Methodology: A retrospective cohort study of prospectively collected data was conducted at St Mark's hospital, London, United Kingdom, for patients diagnosed with EOCRC who underwent at least one episode of post-CRC colonoscopic surveillance between 1978 and 2022. We collected clinicopathological data including tumour molecular status and neoplasia detection rates., Results: In total, 908 colonoscopic surveillance procedures were performed in 195 patients over 2581.3 person-years of follow-up. The diagnostic yields of metachronous CRC, advanced adenomas and non-advanced adenomas were 1.76%, 3.41% and 22.69% respectively. Sixteen patients (8.21%) developed metachronous CRC, and the majority (87.5%) were detected more than 3 years post index EOCRC diagnosis. Detection of advanced neoplasia was significantly higher in EOCRC patients with Lynch syndrome (26.15%) compared with those in whom Lynch syndrome was excluded (13.13%) (OR, 2.343; 95% CI, 1.014-5.256; p = 0.0349)., Conclusions: During colonoscopic surveillance post-EOCRC resection, the long-term risk of developing metachronous advanced neoplasia remains high in the context of Lynch syndrome, but this trend is not as clearly evident when Lynch syndrome has been excluded., (© 2024 The Authors. United European Gastroenterology Journal published by Wiley Periodicals LLC on behalf of United European Gastroenterology.)

Background: Visualization and instrumentation of the frontal sinus is not always possible with a Draf III or modified endoscopic Lothrop procedure (MELP), and external incisions can help augment exposure. We compare lateral frontal sinus access using only a MELP compared to the adjunctive transcaruncular approach and transcutaneous Lynch incision. Methods: Twelve cadaveric heads underwent thin‐cut computed tomography scanning. Measurement of the frontal beak, anteroposterior depth of the frontal sinus, and interorbital distance was performed. There were 4 specimens with poorly pneumatized frontal sinuses that were excluded from the study. Eight cadaveric heads (16 sides) were dissected and a MELP with bilateral transcaruncular and Lynch incisions for access to the lateral frontal sinus was performed. Under image guidance, measurements extended from the midline crista galli to the most lateral point of the frontal sinus visualized using a 0‐degree endoscope with straight suction and a 30‐degree endoscope with curved suction. Results: The proportion of the ipsilateral frontal sinus accessed through the contralateral nare with a 0‐degree endoscope and straight suction using a MELP only, a MELP with transcaruncular approach, and a MELP with Lynch incision, respectively, averaged 41.6%, 51.6%, and 58.9% on the right, and 48.9%, 47.1%, and 61.2% on the left. Using a 30‐degree endoscope and curved suction the proportion accessed using a MELP only, a MELP with transcaruncular approach, and a MELP with Lynch incision, respectively, increased to 76.1%, 62.6%, and 91.8% on the right, and 83.2%, 62.7%, and 88.7% on the left. Conclusion: Adjunctive external approaches can improve access and instrumentation of the frontal sinus when combined with a MELP. [ABSTRACT FROM AUTHOR]

Lynching is a form of extrajudicial execution by hanging carried out by mob, which is functioning independently of local police and law enforcement authorities. Indian also faced Indian WhatsApp lynching, which are a spate of Mob-related violence and killing following the spread of rumours, primarily relating to child-abduction and organ harvesting, via the WhatsApp message service. They fall under the category of organised hate crimes. According to the source from internet, it has been observed a rise in mob lynching cases related to cow vigilantism by over 10%. It is important to note that India does not have one comprehensive parliamentary law on mob lynching. Strong provisions of law and speedy convictions in mob lynching cases will act as deterrence for the society. [ABSTRACT FROM AUTHOR]

This article will explore anamorphosis in David Lynch's Mulholland Drive (2001). Appearing almost simultaneously with perspective as a mode of organizing sight in visual art and architecture mainly, anamorphosis was a type of perspective, popular in the sixteenth and seventeenth centuries, in which an image that was severely distorted could become suddenly "legible" if looked at from the correct angle. Among the ways that anamorphosis is evident in Mulholland Drive is its two-part design, which forces viewers to detect a hidden perspective in the first part of the film. Anamorphosis is visible also in the distortive imagery and changes in optical registers, such as the stylized jitterbug scene at the start of the film. Anamorphosis, finally, is noticeable in the form of an anamorphic figure like the Cowboy who casts a haunting pall over the action and who seems to exist both in the world of the film and outside, entering mysteriously or obliquely, at an angle as it were, with no clear, determinable place of origin. An analysis of anamorphosis in Mulholland Drive leads me to argue that an anamorphic drive is central to Lynch's work more generally and that Lynch belongs to a very long tradition in the visual arts dating back to the fifteenth century. [ABSTRACT FROM AUTHOR]

Our current understanding of the genetic mechanisms that underly cancer pathogenesis is rapidly expanding. Hereditary cancer predisposition syndromes are important to recognize for diagnostic and treatment decision-making but also for family members so they will benefit from surveillance and treatment options. This brief review gives primary care and oncology caregivers a summary of the evolution of hereditary cancer predisposition syndromes, indications for consideration of testing and therapy of patients and families. [ABSTRACT FROM AUTHOR]

The act of lynching in the United States was in fact a form of domestic terrorism perpetrated against darker-skinned Americans. Historians have been pressed to acknowledge the lynching of African-Americans particularly in the Bible-belt South in such states as Mississippi and Alabama. The history of Mexican-Americans lynched by Anglo mobs has been for the most part, ignored by Western historians. Said ignored transgressions occurred frequently in border-states including Texas. Approximately 40 years before the lynching of 14-year-old African-American Emmett Till was the lynching of 14-year-old Mexican-American Antonio Gómez. Both were boys accused of Anglo disrespect. Buried in historical archives, the lynching of Gómez was a Mexican-American manifestation of Anglo colorism. Once informed, social scientists and the U.S. society at-large must then readily admit they lynched Mexican-Americans too! [ABSTRACT FROM AUTHOR]

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City image and self identity are two interrelated notions. Self identity, also referred to as urban related identity, is not solely derived from the physical characteristics of an urban space, but, consists of the social construction founded in the perception of individuals and groups (Lalli & Ploger, 1991). The relationship of the individual with a place is essential as place and space shape human experiences (Chen, 2012). With the trend of gated residential areas emerging in large cities such as Cairo and Alexandria in the late 90s creating a spatial discontinuity and urban fragmentation, this research is examining how open and gated urban residential areas shape place image of New Cairo’s Third Settlement residents.

Founder pathogenic variants (PVs) are prevalent in Israel. This study investigated the current practice of offering cancer patients two-step genetic testing, starting with targeted testing for recurring founder PVs, followed, if negative, by next-generation sequencing. A total of 2128 subjects with cancer or a positive family history underwent oncogenetic testing with a panel of 51 recurring PVs at a tertiary medical center in March 2020-January 2023. Those with a known familial PV (n = 370) were excluded from the analysis. Among the remainder, 128/1758 (7%) were heterozygous for at least one variant, and 44 (34%) carried a PV of medium-high penetrance (MHPV). Cancer was diagnosed in 1519/1758 patients (86%). The diagnostic yield of founder MHPV testing was 2% in cancer patients and 4% in healthy individuals with a positive family history. It was higher in Ashkenazi Jews than non-Ashkenazi Jews and Arabs, but not over 10% for any type of cancer, and it was significantly higher in younger (<40 years) than older (>50 years) individuals (7% vs. 1%). Eighty-four of the heterozygotes (66%), mostly Ashkenazi Jews, harbored a low-penetrance variant (LPV) not associated with the diagnosed cancer, usually APC c.3902T>A. These findings question the advantage of two-step testing. LPVs should not be included in targeted testing because this can lead to an overestimation of the yield, and their detection does not preclude further comprehensive testing.

Lewis Mumford in The City in History (first edition in 1961) emphasises that the structure of modern cities is partially responsible for many social problems seen in Western society. Urban planning should concentrate on an organic relationship between people and their living spaces. The city is a product of Earth, a fact of nature, man’s method of expression, Mumford writes in his The Culture of Cities (first edition in 1938). This also means that both the designer and the user must have a high degree of creativity in order to design and utilise the built environment. By analysing the definition of the city Mumford examines its changes during history from ancient times to recent planning method. He criticises the most dominant design processes of the 20th century: the functionalist and mechanical urban design. He is an advocate of the organic method in planning and understanding cities. The organic approach requires an active and creative approach as opposed to mere passive reception.This organic approach by Mumford to understanding cities is based on the theory of Kevin A. Lynch. We may distinguish 3 normative ways of city planning theory: (1) the cosmic, (2) the mechanic and (3) the organic model.In my paper I will first apply the onion model of culture developed by Geert Hofstede for the city and its analysis, and also for the appearance of creativity in them. After that I am going to examine the city with a special, architectural based mind map theory: the five elements by Lynch. Lynch suggests that these five elements (paths, edges, districts, nodes, landmarks) create the mental map for readability. Finally, I will investigate a usage of mental map in modern city planning (Le Corbusier) and works on the process of “debabelisation” (Otto Neurath). Santrauka Lewisas Mumfordas Mieste istorijoje (pirmasis leidimas – 1961 m.) pabrėžia, kad šiuolaikinių miestų struktūrai tenka dalis atsakomybės dėl daugelio socialinių problemų, regimų Vakarų visuomenėje. Miesto planavimas turėtų būti koncentruojamas į organišką ryšį tarp žmonių ir jų gyvenamųjų erdvių. Miestų kultūroje (pirmasis leidimas – 1938) Mumfordas rašo, kad miestas – tai Žemės produktas, gamtos įvykis, žmogiškosios išraiškos metodas. Tai taip pat reiškia, kad tiek projektuotojas, tiek vartotojas turi būti itin kūrybiškas, idant suprojektuotų ir panaudotų sukurtą aplinką. Analizuodamas miesto apibrėžimą, Mumfordas nagrinėja jo kaitą istorijoje nuo antikos laikų iki dabartinio planavimo metodo. Jis kritikuoja XX a. labiausiai įsivyravusius projektavimo procesus: funkcionalistinį ir mechaninį miesto projektavimą. Jis yra organinio metodo, taikomo miestams planuoti ir suprasti, šalininkas. Organiškas požiūris reikalauja aktyvaus ir kūrybiško požiūrio, priešpriešinamo grynai pasyviam suvokimui.Šis organiškas Mumfordo požiūris, suprantant miestus, grindžiamas Kevino A. Lyncho teorija. Galime išskirti tris normatyvinius miesto planavimo teorijos būdus: 1) kosminį; 2) mechaninį; 3) organinį modelį.Straipsnyje pirmiausia taikomas svogūninis kultūros modelis, kurį miestui ir jo analizei, taip pat jų kūrybiškumo pasireiškimui sukūrė Geertas Hofstede. Paskui nagrinėjamas miestas, pasitelkiant ypatingą, architektūra grindžiamą proto žemėlapio teoriją – penkis Lyncho elementus. Lynchas teigia, kad šie penki elementai (takai, pakraščiai, rajonai, susikirtimo taškai, peizažai) kuria mentalinį reglamentavimo žemėlapį. Galiausiai tyrinėjama, kaip proto žemėlapis naudojamas šiuolaikiniam miestui planuoti (Le Corbusier) ir kokią įtaką daro „debabilizacijos“ procesui (Otto Neurathas). Reikšminiai žodžiai: miesto planavimas, kūrybiškumas, Hofstede, Lynchas, mentalinis žemėlapis, miesto projektavimas, vizualinis argumentavimas.