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Abstract Cholangiocarcinoma (CCA) is a rare biliary tract cancer with a low five-year survival rate and high recurrence rate after surgical resection. Currently treatment approaches include systemic chemotherapeutics such as FOLFIRINOX, a chemotherapy regimen is a possible treatment for severe CCA cases. A limitation of this chemotherapy regimen is its toxicity to patients and adverse events. There exists a need for therapies to alleviate the toxicity of a FOLFIRINOX regimen while enhancing or not altering its anticancer properties. Cold atmospheric plasma (CAP) is a technology with a promising future as a selective cancer treatment. It is critical to know the potential interactions between CAP and adjuvant chemotherapeutics. In this study the aim is to characterize the efficacy of FOLFIRINOX and CAP in combination to understand potential synergetic effect on CCA cells. FOLFIRINOX treatment alone at the highest dose tested (53.8 µM fluorouracil, 13.7 µM Leucovorin, 5.1 µM Irinotecan, and 3.7 µM Oxaliplatin) reduced CCA cell viability to below 20% while CAP treatment alone for 7 min reduced viability to 3% (p

Big data processing systems often employ batched updates and data sketches to estimate certain properties of large data. For example, a CountMin sketch approximates the frequencies at which elements occur in a data stream, and a batched counter counts events in batches. This article focuses on correctness criteria for concurrent implementations of such objects. Specifically, we consider quantitative objects, whose return values are from an ordered domain, with a particular emphasis on (ϵ, δ )-bounded objects that estimate a numerical quantity with an error of at most ϵ with probability at least 1 − δ. The de facto correctness criterion for concurrent objects is linearizability. Intuitively, under linearizability, when a read overlaps an update, it must return the object’s value either before the update or after it. Consider, for example, a single batched increment operation that counts three new events, bumping a batched counter’s value from 7 to 10. In a linearizable implementation of the counter, a read overlapping this update must return either 7 or 10. We observe, however, that in typical use cases, any intermediate value between 7 and 10 would also be acceptable. To capture this additional degree of freedom, we propose Intermediate Value Linearizability (IVL), a new correctness criterion that relaxes linearizability to allow returning intermediate values, for instance, 8 in the example above. Roughly speaking, IVL allows reads to return any value that is bounded between two return values that are legal under linearizability. A key feature of IVL is that we can prove that concurrent IVL implementations of (ϵ, δ )-bounded objects are themselves (ϵ, δ )-bounded. To illustrate the power of this result, we give a straightforward and efficient concurrent implementation of an (ϵ, δ )-bounded CountMin sketch, which is IVL (albeit not linearizable). We present four examples for IVL objects, each showcasing a different way of using IVL. The first is a simple wait-free IVL batched counter, with O(1) step complexity for update. The next considers an (ϵ, δ )- bounded CountMin sketch and further shows how to relax IVL using the notion of r -relaxation. Our third example is a non-atomic iterator over a data structure. In this example, we augment the data structure with an auxiliary history variable state that includes “tombstones” for items deleted from the data structure. Here, IVL semantics are required at the augmented level. Finally, using a priority queue, we show that some objects require IVL to be paired with other correctness criteria; indeed, a natural correctness notion for a concurrent priority queue is IVL coupled with sequential consistency. Last, we show that IVL allows for inherently cheaper implementations than linearizable ones. In particular, we show a lower bound of Ω(n) on the step complexity of the update operation of any wait-free linearizable batched counter from single-writer multi-reader registers, which is more expensive than our O(1) IVL implementation. [ABSTRACT FROM AUTHOR]

Studies have underscored the complexity of psychotherapy for Ultra-Orthodox Jews, and cross-cultural therapy in particular, which evokes fear of disruption of basic values. Parents’ sense of responsibility for their child’s religious education exacerbates these problems in child therapy. However, there is scant research on child therapy for the Ultra-Orthodox, especially in the field of arts therapies. The present study examined the perceptions of 17 Ultra-Orthodox parents whose children were receiving arts therapies (including art therapy, dance/movement therapy, music therapy, psychodrama and bibliotherapy). Semi-structured interviews were conducted with the parents and analyzed based on the principles of Consensual Qualitative Research. The study covered five domains: (1) The parents’ experiences in therapy; (2) The parents’ perceptions of the child’s experiences in therapy; (3) Implications of environmental-social factors on the parents’ perceptions and experiences of therapy; (4) Effects of intercultural aspects on therapy; (5) Perceptions of the use of the arts in therapy. The findings show that the experiences of ultra-Orthodox parents in the arts therapies of their children is complex due to the influence of the socio-cultural context, which involves dealing with stigma and tensions in their relationship with the education system. This context also shapes their perceptions of therapy, which can be characterized as purpose-oriented. The findings also highlight the parents’ challenges in coping with the intercultural therapeutic relationship, and emphasizes the parents’ preference for a therapist from a similar religious/cultural background and for cultural supervision of therapy. However, the results also suggest that there are benefits inherent to intercultural therapy in general and arts therapies in particular, including a sense of security, openness and acceptance of the parents and children.

Background: Bariatric and metabolic surgery (BMS) is an effective treatment for patients with severe obesity. Patients with higher body mass index (BMI) and patients undergoing revisional surgery have a higher rate of major complications. This study purpose is to evaluate perioperative outcomes of patients with BMI ≥ 50 kg/m2. Materials and Methods: A retrospective analysis of patients with a BMI ≥ 50 kg/m2 undergoing BMS between 2015 and 2023 was conducted. A comparative analysis was performed between patients undergoing primary versus revisional surgery. Results: A total of 263 patients were included in the study. Primary procedures were performed in 220 patients (83.7%) and revisional procedures in 43 patients (16.3%). BMS included one anastomosis gastric bypass (n = 183), sleeve gastrectomy (n = 63), and other procedures (n = 17). Mean BMI was 54.6 with no difference between groups. There was no difference in baseline characteristics except the revisional group was older (44.8 ± 9.6 versus 39 ± 13 years; p = 0.006), had higher rates of gastroesophageal reflux disease (21% vs 7.3%; p = 0.005), and fatty liver disease (74% vs 55%; p = 0.02). There was perioperative mortality in three cases (1.1%) with no significant difference between groups. Leak rates were higher, and length of stay (LOS) was longer in the revisional group (4.6% vs 0.45%; p = 0.018 and 2.9 vs 3.7; p = 0.006, respectively). Conclusion: Revisional BMS in patients with a BMI ≥ 50 kg/m2 is associated with increased leak rates and LOS. Mortality rate is 1.1% and is insignificantly different between groups. Further prospective and large-scale studies are needed to clarify the optimal surgical approach to patients with extreme BMI including revisional surgery. [ABSTRACT FROM AUTHOR]

This article examines the dynamics of inter-referencing between cities and develops the concept of the 'Urban Referencing Network' as a representation of the references made by cities to one another in policy documents. The study employs public art policies, specifically the Percent for Art policy, to investigate the structure of inter-referencing within the urban referencing network. Using a corpus of policy documents from 26 Anglophone cities with over one million residents, we analyse 150 documents containing 2178 inter-references. Combining network measurements and regressions, we explore the emergence of central nodes and the mechanisms influencing their formation. The broader field of arts and cultural policies, with its extensive inter-urban connections and professional networks, provides fertile ground for studying urban referencing networks. By integrating literature on policy mobility and urban networks, this study contributes to a deeper understanding of the circulation of urban ideas and the interplay between cities in policy-making processes. The results demonstrate that only a few cities, including New York, Chicago, London, Seattle, Los Angeles, and Montreal, emerge as central nodes, attracting the other cities' attention. Attributes of the referenced cities, like economic importance, iconicity and early adoption, determine to a great extent who are the most central nodes. [ABSTRACT FROM AUTHOR]

Background: The extremely obese patient deserves special consideration: significant comorbidities, technical difficulties, and increased postoperative morbidity and mortality are all expected in this patient population. The study compared early postoperative complications (≤30‐day) following one‐anastomosis gastric bypass (OAGB) morbidity in patients with morbid obesity class IV obesity, body mass index (BMI) ≥50–59.9 kg/m2, and class V obesity, BMI ≥60 patients. Methods: We retrospectively reviewed perioperative OAGB outcomes in three BMI groups. Operative time, length of stay (LOS), and overall early postoperative complication rates were studied. Patient‐reported complications were ranked by Clavien–Dindo Classification (CDC). Results: Between January 2017–December 2021, consecutive patients with obesity class III (n = 2950), IV (n = 256), and V (n = 23) underwent OAGB. BMI groups were comparable in sex, age, and associated comorbidities. Mean operative time was significantly longer in the higher BMI groups: class III (66.5 ± 25.6 min), IV (70.5 ± 28.7 min), and V (80.0 ± 34.7 min), respectively (p = 0.018); no difference in LOS. In respective BMI classes, ≤30‐day complication rates were 3.2%, 3.5%, and 4.3% (p = 0.926). The respective number of patients with CDC grades of one to two were 45 (1.5%), 6 (2.3%), and 1 (4.3%), p = 0.500; and in grade ≥3a, 25 (0.8%), 1 (0.4%), 0 (0.0%), p = 0.669. There was 0.06% mortality (n = 2 in 3229), both in BMI class III. Conclusions: OAGB is a safe BS procedure in patients with class III, IV, and V obesity in the perioperative term with comparable ≤30‐day morbidity in the three BMI groups. [ABSTRACT FROM AUTHOR]

Background and objective: Chronic cough (CC) is a prevalent yet underexplored medical condition, with limited real-world data regarding its healthcare burden. This study investigates the epidemiology, associated comorbidities, and healthcare service utilization among patients with CC. Methods: In this retrospective cohort study, adult patients with at least 3 physician diagnoses of cough over a period spanning a minimum of 8 weeks and a maximum of 12 months anytime between 2009 and 2018, were defined as patients with CC (PwCC). The reference group were adults without cough matched in a 1:1 ratio for age, sex, and place of residence. Results: The study included 91,757 PwCC, reflecting a prevalence of 5.5%. Of those, 59,296 patients (mean [SD] age, 53.9 [16.8] years; 59.6% females) were first diagnosed with CC during the study period, representing a 10-year incidence rate of 3.26% (95%CI: 3.24–3.29%). Diseases associated with the highest OR for CC included lung cancer (OR = 3.32; 95%CI: 2.90–4.25), whooping cough (OR = 3.04; 95%CI: 2.70–3.60), and respiratory infections (OR = 2.81; 95%CI: 2.74–2.88). Furthermore, PwCC demonstrated increased healthcare service utilization, leading to a higher adjusted annual estimated mean cost (USD 4038 vs. USD 1833, p < 0.001). Conclusions: Chronic cough emerges as a relatively prevalent complaint within community care, exerting a considerable economic burden. This study underscores the need for heightened awareness, comprehensive management strategies, and resource allocation to address the multifaceted challenges associated with chronic cough. [ABSTRACT FROM AUTHOR]

Abstract A few modes of perioperative local analgesia have been studied in order to reduce postoperative pain after laparoscopy, including preemptive local anesthetics in the trocar sites and intraperitoneal anesthetics administration at the end of the surgery. However, the evidence regarding their efficacy are conflicting. In addition, the combination of both aforementioned methods has been rarely studied. Our aim was to evaluate whether subcutaneous trocar site and/or intraperitoneal analgesia reduce pain after gynecologic operative laparoscopy. This was a single-centered, randomized, controlled, double-blinded trial. The patients were randomly assigned to one of four equally sized groups: group 1—subcutaneous and intraperitoneal analgesia; group 2—subcutaneous analgesia and intraperitoneal placebo; group 3—subcutaneous placebo and intraperitoneal analgesia; Group 4—subcutaneous and intraperitoneal placebo. The patients, the surgeons, and the pain evaluators were all blinded to the patient’s allocation. Included were patients who underwent elective operative laparoscopy. Exclusion criteria were: active infection, pregnancy, known sensitivity to Bupivacaine-Hydrochloride, chronic pelvic pain, surgeries with additional vaginal procedures, conversion to laparotomy, and malignancy. A total of 9 ml of Bupivacaine-Hydrochloride (Marcaine) 0.5%, or Sodium-Chloride 0.9%, as a placebo, were injected subcutaneously to the trocar sites (3 ml to each trocar site), prior to skin incision. In addition, 10 ml of Bupivacaine-Hydrochloride 0.5%, diluted with 40 ml of Sodium-Chloride 0.9% (a total of 50 ml solution), or 50 ml of Sodium-Chloride 0.9%, as a placebo, were injected intraperitoneally at the end of the surgery. By utilizing the 10 cm Visual-analogue-scale (VAS) we assessed post-operative pain at rest at 3, 8, and 24 h, and during ambulation at 8 and 24 h. The study was approved by the local Institutional Review Board and has been registered at clinicaltrials.gov. We conformed to the CONSORT recommendations. Between December 2016 and July 2019, a total of 119 patients were included in the study. Demographic and interventional characteristics were similar among the groups. The level of postoperative pain, either at rest or with change of position, was not significantly different between the groups, at all-time points. Application of subcutaneous and/or intraperitoneal analgesia is not effective in reducing pain after gynecologic operative laparoscopy. Clinical trial identification number: NCT02976571. Date of trial registration 11/29/2016. URL of the registration site: https://clinicaltrials.gov .

Background: Polychlorinated biphenyls (PCBs) are persistent organic pollutants banned for use worldwide. Due to their biodegradation resistance, they accumulate along the food chain and in the environment. Maternal exposure to PCBs may affect the fetus and the infant. PCBs are immunotoxic and may damage the developing immune system. PCBs are associated with elevated IgE antibodies in cord blood and are considered to be predictive of atopic reactions. Several studies on the association between prenatal exposure to PCBs and atopic reactions were previously published, albeit with conflicting results.Objectives: To examine the association between maternal PCBs levels and atopic reactions in their offspring.Methods: During the years 2013–2015, a prospective birth cohort was recruited at the delivery rooms of Shamir Medical Center (Assaf Harofeh) and “Dana Dwek” Children’s Hospital. Four PCBs congeners were investigated: PCBs 118, 138, 153, and 180. In 2019, when children reached the age of 4–6 years, mothers were interviewed using the ISAAC questionnaire to assess symptoms of atopic reactions, including asthma, allergic rhinitis, and atopic dermatitis.Results: One hundred and fifty mother-child dyads were analyzed. No significant differences were found in the median serum PCBs concentrations of each studied congener or total PCBs for asthma, allergic rhinitis, atopic dermatitis diagnosis, or parent-reported symptoms. No association was found between exposure to total PCBs and the risk for asthma symptoms or diagnosis, adjusted to maternal age and family member with atopic condition: aOR = 0.94, 95%CI: (0.88; 0.99). No association was observed between each studied PCB congener and asthma symptoms or diagnosis. The same results were found also for other studied outcomes—allergic rhinitis and atopic dermatitis.Conclusion: Our study joins a series of previous studies that attempt to shed light on environmental exposures in utero as influencing factors for atopic conditions in children. Our results reflect the complexity of the pathophysiology of these phenomena. No relationship between maternal serum PCBs levels was demonstrated for asthma, allergic rhinitis, or atopic dermatitis. However, additional multi-participant studies, with longer, spanning into later pediatric age follow up are needed.

Plasma‐based biomedical applications rely on the reactive oxygen and nitrogen species generated in cold atmospheric plasmas, where complex chemical kinetic schemes occur. The optimization of plasma medicine is thus required for each specific biomedical purpose. In the view of pharmacology, it is to optimize the active pharmaceutical ingredients. This work is thus the first attempt of such a complex task utilizing the recent development of machine learning technologies. Herein, a general method of passive plasma chemical diagnostics and optimization in real time is proposed. Based on spontaneous emission spectroscopy, an artificial neural network provides the gas chemical compositions along with other information such as temperatures. The information further passes through the second neural network which outputs the adjustments of external control inputs including energy, gas injections, and extractions to optimize the plasma chemistry.

Background: Polychlorinated biphenyls (PCBs) are ubiquitous environmental contaminants found in human tissues. PCBs can be transferred through the placenta and may disrupt the maternal thyroid homeostasis, and affect fetal thyroid hormone production. Several studies have shown that intrauterine exposure to PCBs might be associated with abnormal levels of thyroid hormones in mothers and their offspring.Objectives: To examine the associations between environmental exposure to PCBs and thyroid hormone levels in mothers and newborns.Methods: The EHF-Assaf-Harofeh-Ichilov cohort includes 263 mothers-newborns dyads. A total of 157 mother-newborn dyads had both PCBs and thyroid function measures. Regression models were used to estimate associations between maternal PCB exposure and maternal and newborn thyroid function, controlling for possible confounders.Results: Four PCBs congeners were analyzed: PCBs 118, 138, 153, and 180. ∑PCBs median (IQR) level was 14.65 (2.83–68.14) ng/g lipids. The median maternal thyroid-stimulating hormone (TSH) level was 2.66 (0.70–8.23) μIU/ml, the median maternal free thyroxine (FT4) level was 12.44 (11.27–13.53) μg/dL, the median maternal thyroid peroxidase antibodies (TPO Ab) level was 9.6 (7.36–12.51) IU/mL. Newborns' median total thyroxine (T4) level was 14.8 (7.6–24.9) μg/dL. No association was found between exposure to different congeners or to ∑PCBs and maternal TSH, FT4, thyroglobulin autoantibodies (Tg Ab), TPO Ab and newborn total T4 levels. In multivariable analysis a 1% change in ∑PCBs level was significantly associated with a 0.57% change in maternal TSH levels in women with body mass index (BMI) < 19. The same association was observed for each of the studied PCB congeners. Maternal TPO Ab levels statistically significantly increased by 0.53 and 0.46% for 1% increase in PCB 118 and 153 congeners, respectively. In women with BMI > 25, the association between the PCBs levels and maternal TSH levels was in the opposite direction. No association was found in women with normal BMI (19–24.9).Conclusions: Background exposure to environmentally relevant concentrations of some PCBs can alter thyroid hormone homeostasis in pregnant women and might be associated with abnormal TSH levels and TPO-Ab in women with low BMI. However, these findings require further investigation.