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The Ural type of the domestic black-and-white breed is distinguished by high productivity indicators, good suitability for use in the conditions of industrial milk technology. To obtain modern dairy cattle, related breeds were used in the herds, a significant number of animals obtained as a result of closely related breeding were revealed. the study of the influence of the degree of inbreeding on the growth and development of repair young is relevant and has practical significance. It was found that the live weight of heifers in all accounting periods practically did not differ, that is, it can be said that the method of obtaining heifers using unrelated or related selection did not affect the dynamics of live weight during their cultivation. The average daily gains in live weight differed slightly by growth periods and by groups. So they were higher in the periods from the first to the first fruitful insemination and from 10 to 12 months, lower gains were noted in the period from the moment of fruitful insemination to 18 months of age. The highest milk yield for lactation was obtained from the first heifers with a remote degree of inbreeding.

Nga Yu Cheung, Anna Gorelik, Parag Mehta, Louis Mudannayake, Arundati Ramesh, Thayyllathil Bharathan, Gregory GoldenbergDepartment of Medicine, New York Presbyterian Brooklyn Methodist Hospital, Brooklyn, NY, USABackground: With growing expense in chronic illness and end-of-life (EOL) care, population-based interventions are needed to reduce the health care cost and improve patients’ quality of life. The authors believe that promotion of palliative medicine is one such intervention and this promotion depends on the acceptance of palliative medicine concepts by health care professionals.Aims of the studies: Perception of palliative medicine in chronic illness and in EOL care by health care professionals was learned in two studies carried out at a teaching community hospital 14 years apart.Participants and methods: Voluntary and anonymous surveys were randomly distributed among physicians, nurses, and social workers/case managers. Participants in the two studies presented two different groups of health care providers.Results of the studies: Results of the two studies were essentially similar. On most of the issues, respondents’ perceptions were consistent with palliative medicine concepts and confidence in palliation grew over the 14-year period. The authors call this approach a “palliative attitude.” Physicians with greater experience performed better in care planning. Younger physicians were more perceptive to withdrawal of care in futile cases. Participants’ religion had no influence on perception of palliative medicine. Attendance of educational activities did not influence attitudes of health care professionals. Health care providers who favored involvement of palliative care teams in patients’ management were better in care planning, interpretation of the DNR consent, use of opioids at the EOL, use of intensive care, and evaluation of the disease trajectory.Conclusion: The authors conclude that direct interaction between palliative and interdisciplinary teams in clinical practice is the key factor in the education of health care professionals, in the development of a “palliative attitude,” and in the promotion of palliative medicine.Keywords: health care professionals, end-of-life care, chronic illness, palliative care concepts, palliative attitude

The article presents a physical and mathematical model developed by the authors. The model allows analyzing the amplitude-frequency characteristic (AFC) of electroencephalograms (EEG) of a human brain. The proposed method of EEG processing, in contrast to the previously used one, is based on approximating the AFC by an equation that contains a set of coefficients. This method is convenient for comparing data obtained from different subjects and, as found, has diagnostic significance. Previously, only the frequency / amplitude ratio or its inverse was used for evaluations. The results achieved indicate the possibility of differentiating patients of various neuropsychic profiles according to the values of the parametric indicators obtained by approximating the EEG amplitude-frequency response.

OBJECTIVE: To review new drugs and devices relevant to otolaryngology approved by the Food and Drug Administration (FDA) in 2022. DATA SOURCES: Publicly available FDA data on drugs and devices approved in 2022. REVIEW METHODS: A preliminary screen was conducted to identify drugs and devices relevant to otolaryngology. A secondary screen by members of the American Academy of Otolaryngology-Head and Neck Surgerys (AAO-HNS) Medical Devices and Drugs Committee differentiated between minor updates and new approvals. The final list of drugs and devices was sent to members of each subspecialty for review and analysis. CONCLUSION: A total of 1251 devices and 37 drugs were identified on preliminary screening. Of these, 329 devices and 5 drugs were sent to subspecialists for further review, from which 37 devices and 2 novel drugs were selected for further analysis. The newly approved devices spanned all subspecialties within otolaryngology. Many of the newly approved devices aimed to enhance patient experience, including over-the-counter hearing aids, sleep monitoring devices, and refined CPAP devices. Other advances aimed to improve surgical access, convenience, or comfort in the operating room and clinic. IMPLICATIONS FOR PRACTICE: Many new devices and drugs are approved each year to improve patient care and care delivery. By staying up to date with these advances, otolaryngologists can leverage new innovations to improve the safety and quality of care. Given the recent approval of these devices, further studies are needed to assess long-term impact within the field of otolaryngology.

In 2002, a new Ural type of black-and-white breed was officially registered. Animals of this type have high productivity indicators, but at the same time there is a decrease in the productive longevity of the breeding stock. The conjugacy of milk yield for lactation is established, which allows for the first lactation to carry out selection fory milk yield. The relationship of milk yield for the first lactation weakens with the age of the animals and becomes negative for the fifth lactation. The conjugacy of such characteristics as milk yield per lactation and fat mass fraction in milk varies both by lactation and relative to milk yield per lactation. The conjugacy between milk yield and protein in milk for lactation was negative with fluctuations from low to medium-negative. For 5 lactation, there is a high positive relationship between milk yield for the first lactation and protein mass fraction in milk for 5 lactation. There are fluctuations in the correlation coefficients for fat mass fraction in milk for lactations, the conjugation of the trait with each other remains positive in the period from the first to the 4 lactation, excluding the correlation coefficient of this indicator between 1 and 5 lactation.

Safely expanding indications for cellular therapies has been challenging given a lack of highly cancer-specific surface markers. Here we explore the hypothesis that tumor cells express cancer-specific surface protein conformations that are invisible to standard target discovery pipelines evaluating gene or protein expression, and these conformations can be identified and immunotherapeutically targeted. We term this strategy integrating cross-linking mass spectrometry with glycoprotein surface capture 'structural surfaceomics'. As a proof of principle, we apply this technology to acute myeloid leukemia (AML), a hematologic malignancy with dismal outcomes and no known optimal immunotherapy target. We identify the activated conformation of integrin β2 as a structurally defined, widely expressed AML-specific target. We develop and characterize recombinant antibodies to this protein conformation and show that chimeric antigen receptor T cells eliminate AML cells and patient-derived xenografts without notable toxicity toward normal hematopoietic cells. Our findings validate an AML conformation-specific target antigen and demonstrate a tool kit for applying these strategies more broadly.

Abstract Background In 2017, we published an article addressing drug shortages (DS) in Israel, exploring regulatory perspectives, challenges, and potential solutions. Since then, DS remain a significant concern for patients, healthcare providers, and policymakers globally. In this updated article, we revisit the topic, providing new insights, data, and analysis on the current DS landscape in Israel, efforts to mitigate them, and propose strategies to combat this escalating issue. Methods We conducted a comprehensive search of the Israeli Ministry of Health (MOH) DS database, spanning from 2014 to the present. We extracted DS numbers and their reasons. Further searches on the Israeli MOH website, pharmaceutical division archives, and the internet yielded official MOH publications and correspondence regarding regulatory responses to DS from 2017 onwards. Additionally, two specific cases of DS were examined to analyze their handling. Recent activities and publications from the Israeli MOH aimed at reducing DS were also reviewed. Results Between 2014 and 2022, DS surged 2.66-fold. Total DS were 3228; 672 due to commercial reasons, and 2556 to operational reasons (20.5% and 79.5% respectively). The average duration of intermittent DS increased 1.56-fold, from 85 to 133 days. Manufacturers informed the MOH 22 days prior to actual shortage on average. Analyzing 2022's DS (640) by ATC groups, prominent categories included nervous system drugs (18%), drugs acting on the alimentary tract and metabolism (14%), and dermatologicals (11%). Operational DS in 2022 (n = 564) were primarily due to stock delivery delays (38%), stock over-utilization (12%), and raw material shortages (9%). Sixteen official MOH publications on DS were identified from 2017 onwards. Moreover, two high-impact DS case studies were examined. Conclusion Despite routine monitoring by the Israeli MOH and updating the DS policy throughout this period, DS persist, intensifying annually and posing serious health risks. This trend mirrors international patterns, affecting countries globally. In Israel's uniquely structured healthcare system, with its swift stakeholder cooperation and implementation capabilities, more effective DS management is conceivable. We propose ten universally applicable rules to address DS challenges.

Abstract The majority of human genetic diseases are caused by single nucleotide variants (SNVs) in the genome sequence. Excitingly, new genomic techniques known as base editing have opened efficient pathways to correct erroneous nucleotides. Due to reliance on deaminases, which have the capability to convert A to I(G) and C to U, the direct applicability of base editing might seem constrained in terms of the range of mutations that can be reverted. In this evaluation, we assess the potential of DNA and RNA base editing methods for treating human genetic diseases. Our findings indicate that 62% of pathogenic SNVs found within genes can be amended by base editing; 30% are G>A and T>C SNVs that can be corrected by DNA base editing, and most of them by RNA base editing as well, and 29% are C>T and A>G SNVs that can be corrected by DNA base editing directed to the complementary strand. For each, we also present several factors that affect applicability such as bystander and off-target occurrences. For cases where editing the mismatched nucleotide is not feasible, we introduce an approach that calculates the optimal substitution of the deleterious amino acid with a new amino acid, further expanding the scope of applicability. As personalized therapy is rapidly advancing, our demonstration that most SNVs can be treated by base editing is of high importance. The data provided will serve as a comprehensive resource for those seeking to design therapeutic base editors and study their potential in curing genetic diseases.

This work provides a study of methods for the automated derivation of control strategies for over-actuated systems. For this purpose, Reinforcement Learning (RL) and Model Predictive Control (MPC) approximating the solution of the Optimal Control Problem (OCP) are compared using the example of an over-actuated vehicle model executing an ISO Double Lane Change (DLC). This exemplary driving maneuver is chosen due to its critical vehicle dynamics for the comparison of algorithms in terms of control performance and possible automation within a design space exploration framework. The algorithms show reasonable control results for the goal of this study, although there are differences in terms of driving stability. While Model Predictive Control first requires the optimization of the trajectory, which should then be optimally tracked, RL may combine both in one step. In addition, manual effort required to adapt the OCP problem to new design variants for solving it with RL and MPC is evaluated and assessed with respect to its automation. As a result of this study, an Actor-Critic Reinforcement Learning method is recommended for the automated derivation of control strategies in the context of a design space exploration.

Abstract Background Rectal cancer is commonly treated by chemoradiation therapy, followed by the low anterior resection anal sphincter-preserving surgery, with a temporary protecting ileostomy. After reversal of the stoma a condition known as low anterior resection syndrome (LARS) can occur characterized by a combination of symptoms such as urgent bowel movements, lack of control over bowel movements, and difficulty fully emptying the bowels. These symptoms have a significant negative impact on the quality of life for individuals who have survived the cancer. Currently, there is limited available data regarding the presence, risk factors, and effects of treatment for these symptoms during long-term follow-up. Aims To evaluate long term outcomes of low anterior resection surgery and its correlation to baseline anorectal manometry (ARM) parameters and physiotherapy with anorectal biofeedback (BF) treatment. Methods One hundred fifteen patients (74 males, age 63 ± 11) who underwent low anterior resection surgery for rectal cancer were included in the study. Following surgery, patients were managed by surgical and oncologic team, with more symptomatic LARS patients referred for further evaluation and treatment by gastroenterologists. At follow up, patients were contacted and offered participation in a long term follow up by answering symptom severity and quality of life (QOL) questionnaires. Results 80 (70%) patients agreed to participate in the long term follow up study (median 4 years from stoma reversal, range 1–8). Mean time from surgery to stoma closure was 6 ± 4 months. At long term follow up, mean LARS score was 30 (SD 11), with 55 (69%) patients classified as major LARS (score > 30). Presence of major LARS was associated with longer time from surgery to stoma reversal (6.8 vs. 4.8 months; p = 0.03) and with adjuvant chemotherapy (38% vs. 8%; p = 0.01). Patients initially referred for ARM and BF were more likely to suffer from major LARS at long term follow up (64% vs. 16%, p

Abstract Objective In‐office ablation of the posterior nasal nerve (PNN) has emerged as an effective treatment option for chronic rhinitis patients. This study explored questions patients commonly search online regarding this therapy and the quality of content available. Study Design A retrospective analysis of online search criteria and sources was performed with subsequent analysis of results. Setting Search and data acquisition was in September of 2023. Methods Most common search terms related to cryotherapy and radiofrequency neurolysis of the PNN were identified with associated People Also Ask (PAA) questions. Questions were categorized and organized into subtopics and sources evaluated using readability and quality metrics. Results A total of 255 unique PAA questions and 175 unique websites were identified. The most common subtopics were related to facts about chronic rhinitis (26.7%) and rhinitis treatment options (25.1%). Nearly a quarter (24.3%) of websites were from commercial sources. Quality metrics indicate difficult‐to‐read and low‐quality materials. Conclusion Existing online resources need improvement to provide patients material that is easier to read. Physicians counseling patients should be aware of these areas for adequate shared decision making.

Abstract Objectives Posterior nasal nerve (PNN) ablation is a minimally invasive treatment option for patients with chronic rhinitis. Recent evidence shows that parasympathetic innervation of the nasal cavity is more extensive and there are many fibers posterior to the lateral attachment of the middle turbinate. We describe a modified ablative technique that targets the extensive innervation of the posterior nasal nerves. Methods Description of the technique and retrospective cohort analysis. In addition to the traditional radiofrequency and cryoablation targets, three additional treatment sites posterior to the middle turbinate were targeted using radiofrequency ablation, as well as one focused treatment posteroinferior to the middle turbinate attachment using cryotherapy ablation. The primary outcome collected was a 30% improvement in overall rhinitis symptoms. Results Forty‐five patients received treatment and completed 3‐month follow‐up using the modified technique for radiofrequency and cryotherapy PNN ablation. Previously, our institution documented a 64.5% responder rate at 3 months. After introducing the modified technique, the response rate at 3 months significantly improved (64.5% vs. 91.1%, p = .004). Conclusions This report suggests improved efficacy with implementation of the modified technique for in‐office PNN ablation. Given the extensive nature of the post‐ganglionic parasympathetic fibers of the nasal cavity which often emerge posterior to the middle turbinate attachment, a modified technique to target these branches should be considered. Prospective randomized studies comparing this modified technique to the traditional technique are needed. Level of Evidence III.

Objective To compare differences in recruitment and attrition between placebo control randomised trials of surgery, and trials of the same surgical interventions and conditions that used non-operative (non-placebo) controls.Design Meta-epidemiological study.Data sources Randomised controlled trials were identified from an electronic search of MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials from their inception date to 21 November 2018.Study selection Placebo control trials evaluating efficacy of any surgical intervention and non-operative control trials of the same surgical intervention were included in this study. 25 730 records were retrieved from our systemic search, identifying 61 placebo control and 38 non-operative control trials for inclusion in analysis.Outcome measures Primary outcome measures were recruitment and attrition. These were assessed in terms of recruitment rate (number of participants enrolled, as a proportion of those eligible) and overall attrition rate (composite of dropout, loss to follow-up and cross-overs, expressed as proportion of total sample size). Secondary outcome measures included participant cross-over rate, dropout and loss to follow-up.Results Unadjusted pooled recruitment and attrition rates were similar between placebo and non-operative control trials. Study characteristics were not significantly different apart from time to primary timepoint which was shorter in studies with placebo controls (365 vs 274 days, p=0.006). After adjusting for covariates (follow-up duration and number of timepoints), the attrition rate of placebo control trials was almost twice as high compared with non-operative controlled-trials (incident rate ratio (IRR) (95% CI) 1.8 (1.1 to 3.0), p=0.032). The incorporation of one additional follow-up timepoint (regardless of follow-up duration) was associated with reduced attrition in placebo control surgical trials (IRR (95% CI) 0.64 (0.52 to 0.79), p