Voltage-Controlled Magnon Transistor via Tuning Interfacial Exchange Coupling.

Magnon transistors that can effectively regulate magnon transport by an electric field are desired for magnonics, which aims to provide a Joule-heating free alternative to the conventional electronics owing to the electric neutrality of magnons (the key carriers of spin-angular momenta in the magnonics). However, also due to their electric neutrality, magnons have no access to directly interact with an electric field and it is thus difficult to manipulate magnon transport by voltages straightforwardly. Here, we demonstrated a gate voltage (V_{g}) applied on a nonmagnetic metal and magnetic insulator (MI) interface that bent the energy band of the MI and then modulated the probability for conduction electrons in the nonmagnetic metal to tunnel into the MI, which can consequently enhance or weaken the spin-magnon conversion efficiency at the interface. A voltage-controlled magnon transistor based on the magnon-mediated electric current drag (MECD) effect in a Pt-Y_{3}Fe_{5}O_{12}-Pt sandwich was then experimentally realized with V_{g} modulating the magnitude of the MECD signal. The obtained efficiency (the change ratio between the MECD voltage at ±V_{g}) reached 10%/(MV/cm) at 300 K. This prototype of magnon transistor offers an effective scheme to control magnon transport by a gate voltage.

Long-term efficacy and safety of baricitinib in patients with severe alopecia areata: 104-week results from BRAVE-AA1 and BRAVE-AA2.

BACKGROUND: Efficacy of the Janus kinase (JAK) inhibitor baricitinib for severe alopecia areata (AA) continuously increased over 52 weeks in two Phase 3 trials. There are limited long-term data on JAK inhibitors in AA. OBJECTIVES: To evaluate efficacy and safety of baricitinib for severe AA through 104 weeks of continuous therapy. METHODS: Integrated data from the BRAVE-AA1 and BRAVE-AA2 Phase 3 trials included adults with Severity of Alopecia Tool (SALT) scores ≥50 (≥50% scalp hair loss) randomized to and continuously treated with 2-mg or 4-mg baricitinib through Week 104. Patients who qualified to remain on continuous treatment included subjects who achieved SALT score ≤20 at Week 52 (Week-52 responders; 2-mg: N = 65; 4-mg: N = 129) and baricitinib 4-mg-treated patients who had SALT score >20 at Week 52 but achieved SALT score ≤20 at prior visit(s) and/or had significant improvement in eyebrow or eyelash hair growth relative to baseline by Week 52 (Week-52 mixed responders; N = 110). Week-104 outcomes included the proportion of patients achieving SALT score ≤20 (≤20% scalp hair loss). Data were censored after treatment discontinuation. RESULTS: Among baricitinib 4-mg-treated and baricitinib 2-mg-treated Week-52 responders, 90.7% and 89.2%, respectively, maintained SALT score ≤20 at Week 104. Among Week-52 mixed responders, 39.1% reached SALT score ≤20 by Week 104. Continued improvement in eyebrow and eyelash regrowth was observed across groups. The most frequent treatment-emergent adverse events were COVID-19, upper respiratory tract infection, headache, nasopharyngitis, acne, urinary tract infection and creatine phosphokinase increase. CONCLUSIONS: Baricitinib demonstrated a high level of maintenance of efficacy over 104 weeks in patients with severe AA. Efficacy increased in Week-52 mixed responders, illustrating that long-term treatment is necessary to observe maximum benefit in some patients. No new safety signals were observed.

Neuroinflammation in Obese Children.

Obesity is associated with chronic persistent inflammation due to a pool of tissue macrophages that can penetrate the blood-brain barrier and cause neuroinflammation. The analysis of the association of CD14+CD163+ monocytes in the peripheral blood with cognitive functions in 56 obese children (mean age 11.95 (9.45; 14.45) years) was carried out. The control group consisted of 10 children (mean age 10.4 (9.3; 13.8) years). Standard deviation of the body mass index (SDS BMI) and height (SDS height) were calculated using WHO AnthroPlus software (for children of 6-19 years). Body composition was assessed using bioimpedance measurement. Mononuclear cells were isolated from whole blood by centrifugation on a Ficoll-Urografin density gradient (ρ=1.077 g/ml). The content of CD14+CD163+ monocytes in the peripheral blood was assessed by flow cytometry. To analyze cognitive functions, the intelligence coefficient (IQ) was calculated and a Russian adaptation of the Rey test was performed. We found an increase in the number of M2-polarized CD14+CD163+ monocytes in the peripheral blood with an increase in the obesity degree and in the presence of cognitive decline, as well as a negative correlation of the level of M2-polarized monocytes and IQ, taking into account the excess of visceral fat. The revealed data on the relationship of M2-polarized CD14+CD163+ peripheral blood monocytes with obesity in children and the development of neuropsychological deficiency confirm the role of peripheral visceral obesity and neuroinflammation.

Effect of Gonadotropin-Releasing Hormone Antagonist on the Expression Patterns of Insulin-Like Growth Factor 1, Androgen Receptor, and Luteinizing Hormone Receptor in an Experimental Rat Model of Functional Ovarian Cysts.

We studied the expression of insulin-like growth factor 1 (IGF-1), androgen receptor (AR) and luteinizing hormone receptor (LHR) in the ovaries under the conditions of the modeling and subsequent treatment of functional ovarian cysts with gonadotropin-releasing hormone antagonist (ant-GnRH). The intensity of IGF-1, LHR, and AR expression in the generative elements of rat ovaries changed under conditions of functional ovarian cysts simulation, as well as during treatment with ant-GnRH. In both experimental groups, the expression levels of the studied markers in preantral follicles and epithelial lining of cysts were found to be related to the number of growing follicles and cysts. A divergence of LHR and AR expression indices and a more pronounced decrease in the number of cystic cavities were observed in the group receiving ant-GnRH. These changes demonstrate a positive effect of ant-GnRH on intra-ovarian regulatory factors and a therapeutic effect in functional ovarian cysts.

Morphofunctional State of the Ovaries in Rats with Experimental Model of Functional Cysts and Their Treatment with Gonadotropin-Releasing Hormone Antagonist.

The morphofunctional features of the ovaries were evaluated in rats with functional ovarian cysts model treated with gonadotropin-releasing hormone antagonist. Administration of the antagonist significantly (p=0.009) reduced the number of cysts and the growth of follicles in the ovaries. The obtained results attest to a possibility of successful treatment of functional ovarian cysts with gonadotropin-releasing hormone antagonist.

[Intraductal radiofrequency ablation for neoplasms of the major duodenal papilla with intraductal spread]. / Vnutriprotokovaya radiochastotnaya ablyatsiya pri novoobrazovaniyakh bol'shogo sosochka dvenadtsatiperstnoi kishki s vnutriprotokovym rasprostraneniem.

OBJECTIVE: To analyze the efficacy of intraductal radiofrequency ablation (RFA) for neoplasms of the major duodenal papilla with intraductal spread. MATERIAL AND METHODS: Eleven patients with adenomas of the major duodenal papilla and intraductal spread underwent intraductal RFA between 2022 and 2023. Spread to the common bile duct ranged from 10 to 30 mm, to the main pancreatic duct - from 5 to 11 mm. RESULTS: Technical success was achieved in all cases. Complications after intraductal RFA occurred in 4 cases (post-manipulation pancreatitis - 2 cases, repeated intraductal RFA for residual adenomatous growths - 2 cases). Technical success of stenting of the main pancreatic and common bile ducts was achieved in all cases. CONCLUSION: Intraductal radiofrequency ablation for neoplasms of the major duodenal papilla with intraductal spread ensured complete destruction of intraductal tumor with adequate clinical effect and no need for highly traumatic surgery.

[Endoscopic treatment of recurrent Zenker diverticulum and postoperative esophageal stricture]. / Endoskopicheskaya krikofaringoezofagomiotomiya v lechenii patsientki s retsidivnym divertikulom Tsenkera i posleoperatsionnoi strikturoi pishchevoda.

Zenker diverticulum is a rare disease accounting for 1.5-5% of esophageal diverticula. For a long time, surgical treatment of Zenker pharyngoesophageal diverticula implied open diverticulectomy via cervical approach. However, this intervention is characterized by high postoperative morbidity and recurrence rate. Oral endoscopic minimally invasive cricopharyngoesophagomyotomy has become widespread over the past 10 years. We present a 55-year-old female who underwent endoscopic treatment for recurrent Zenker diverticulum and postoperative esophageal stricture. We obtained favorable result in a patient with recurrent Zenker diverticulum after previous open surgeries complicated by esophageal stricture. Endoscopic management eliminated recurrent diverticulum and esophageal stricture, as well as improved the quality of life. Endoscopic approach is preferable for pharynoesophageal diverticula compared to traditional surgical diverticulectomy. Obvious advantages of this technique are stable functional result, low incidence of complications and mortality, short-term postoperative period with fast rehabilitation. Extended myotomy is essential for successful oral endoscopic cricopharyngoesophagomyotomy.

[Intraductal radiofrequency ablation under endosonography and cholangioscopy for residual adenoma of the major duodenal papilla with intraductal component]. / Vnutriprotokovaya radiochastotnaya ablyatsiya pod kontrolem endosonografii i kholangioskopii pri rezidual'noi adenome bol'shogo sosochka dvenadtsatiperstnoi kishki s vnutriprotokovym komponentom. Obzor literatury.

All adenomas of the major duodenal papilla (MDP) require resection regardless of morphological structure due to high risk of malignancy. Currently, intraluminal endoscopic interventions are preferable for these adenomas. MDP neoplasms with intraductal spread (type III and IV) are of particular difficulty for endoscopic techniques. Intraductal radiofrequency ablation provides new opportunities for minimally invasive treatment of patients with MDP adenomas and intraductal component. A 72-year-old patient after previous endoscopic papillectomy for MDP adenoma admitted to the Vishnevsky National Research Medical Center of Surgery due to residual adenomatous growths within the papillectomy zone extending to the common bile duct throughout 13 mm. The patient underwent intraductal RFA under endosonography and cholangioscopy. Despite difficult localization of residual growths extending to the common bile duct, endosonography-guided intraductal RFA provided total destruction of residual tumor that was confirmed by cholangioscopy. Length of treatment was 4 months, relapse-free period - 10 months. Minimally invasive endoscopic technology for residual MDP adenoma provided good clinical results.

[Recovery of consciousness under therapy with benzodiazepines. A case report and literature review]. / Vosstanovlenie yasnogo soznaniya na fone priema benzodiazepinov. Opisanie sluchaya i obzor literatury.

BACKGROUND: Treatment of patients with prolonged and permanent disturbance of consciousness is still an extremely difficult problem. Nowadays, management is based on pathophysiological and molecular mechanisms of impaired consciousness. Several electrophysiological and pharmacological methods were proposed to restore consciousness in appropriate patients. OBJECTIVE: We present recovery of clear consciousness under therapy with phenazepam and literature review devoted to therapy of these disorders. RESULTS AND CONCLUSION: This case confirms available data on drug neuromodulation in complex treatment of patients with prolonged impairment of consciousness and substantiates the need for individual multimodal assessment of structural and functional disorders in prolonged and chronic impairment of consciousness for adequate therapy.

[Physical rehabilitation in sarcopenia: modern approaches. (A literature review)]. / Fizicheskaya reabilitatsiya pri sarkopenii: sovremennye podkhody. (Obzor literatury).

The number of middle-aged and elderly population is increasing every year. At the same time, the course of most chronic diseases worsens with age, which can be explained by significant changes in body composition, including redistribution and increase of fat mass and decrease in muscle and skeletal mass. Thus, a decrease in muscle mass becomes intrinsic for the body from the age of 40 and develops on average by 0.5-1.0% per year. The prevalence of patients with sarcopenia is estimated to be between 11 and 50% in different age groups of population: middle, elderly and senile. In addition, the decline in physical activity associated with the urbanization and automation of labor exacerbates the disease at a younger age, which predicts an increase in the number of such patients in the future. OBJECTIVE: To determine the role of physical rehabilitation in sarcopenia. MATERIAL AND METHODS: A systematic review including studies found in PubMed, MedLine, Scopus and Web of Science Core Collections databases for 2019-2022 was conducted. The used enrollment criteria were the following: systematic reviews, including cross-over or cohort studies targeting at persons aged from 40 to 90 years of both sexes, with available data on sarcopenia, its severe form or other combinations of physical performance markers called sarcopenia. The mandatory parameter for inclusion in the study was the presence of the effectiveness assessment of physical rehabilitation without limiting its parameters. The systematic review was performed in accordance with the recommendations of the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) 2020. RESULTS: The best kind of training are 30-60-minute comprehensive methods with predominance of resistance exercises with minimum duration of the course of 3 months and frequency of 3 inconsistent in-person trainings per week under the supervision of a specialist for patients with sarcopenia in order to increase muscle strength and mass, as well as performance. The intensity should consist of the following parameters: start with fewer sets but more repetitions (12-15) with less intensity (55% of maximum) and move to more sets with less repetition (4-6) and greater intensity (>80% of maximum). CONCLUSION: This article describes the parameters of exercises that are most effective in terms of muscle strength and mass increase and safe for patients. The compilation and further study of this complex in practice are needed.

[Comparative characteristics of oxidative modification intensity of proteins in infant milk formulas].

Cow's milk is mainly used in the production of infant milk formulas. However, the protein composition of cow's milk differs significantly from the proteome of breast milk. In addition, various technological factors significantly affect the properties and structure of proteins, susceptibility to oxidative processes. This article uses a method of complex evaluation of the products of oxidative modification of proteins to characterize the total level of carbonyl compounds with the analysis of the ratio of aldehyde-dinitrophenylhydrazones (ADNPH) and ketone-dinitrophenylhydrazones (CDNPH), which increases the possibility of determining the severity of protein damage. The purpose of the study was to compare the level of indicators of oxidative modification of proteins in adapted milk infant formulas. Material and methods. The research objects were 4 dry adapted milk infant formulas, as well as ultra-pasteurized cow's milk. The intensity of oxidative modification of milk proteins was determined spectrophotometrically by the reaction of carbonyl compounds with dinitrophenylhydrazine (DNFG). Results. With spontaneous oxidation in infant formula, the total area of carbonyl derivatives of proteins (Sомб) was increased compared to the indicators of ultra-pasteurized cow's milk. The greatest change occurred in relation to ADNFG indicators (SАДНФГ), the level of which increased in 3 formulas by 48.6-59.4%. The content of ketone derivatives (SКДНФГ) did not differ significantly in the studied mixtures from milk indicators. The level of carbonyl derivatives of proteins in milk infant formulas was even more elevated during the induction of oxidation by the addition of iron ions and hydrogen peroxide to the incubation medium. The content of both total and various fractions of carbonyl compounds exceeded the corresponding indicators of cow's milk by 2.0-2.6 times. Conclusion. The results of the study indicate a greater susceptibility to oxidative damage of proteins in milk infant formulas, compared with cow's milk.

[Bowel preparation before colorectal surgery].

High quality bowel preparation is a necessary part of preoperative preparation for colorectal surgery and one of the keys to the success of surgery, which directly affects the quality of intraoperative procedures and postoperative recovery of patients. Conventional intestinal preparation mainly includes three aspects: preoperative dietary control, intestinal cleansing and prophylactic use of antibiotics. With the development of evidence-based medicine, the concepts and methods of bowel preparation have also changed. Long fasting is no longer advocated before surgery, and the traditional mechanical bowel preparation are also challenged. This article summarizes the application and research progress of different intestinal preparation methods before colorectal surgery, aiming to provide reference for clinical work of colorectal surgeons.

[High STING expression exacerbates renal ischemia-reperfusion injury in mice by regulating the TLR4/NF-κB/NLRP3 pathway and promoting inflammation and apoptosis].

OBJECTIVE: To investigate renal expression level of STING in mice with renal ischemia-reperfusion injury (IRI) and its regulatory role in IRI. METHODS: C57BL/6 mice were divided into sham operation group, IRI (induced by clamping the renal artery) model group, IRI+DMSO treatment group, and IRI+SN-011 treatment group. Serum creatinine and blood urea nitrogen of the mice were analyzed, and pathological changes in the renal tissue were assessed with PAS staining. RT-qPCR, ELISA, Western blotting, and immunohistochemistry were used to detect the expression levels of STING, KIM-1, Bcl-2, Bax, caspase-3, TLR4, P65, NLRP3, caspase-1, CD68, MPO, IL-1ß, IL-6, and TNF-α in the renal tissues. In the cell experiment, HK-2 cells exposed to hypoxia-reoxygenation (H/R) were treated with DMSO or SN-011, and cellular STING expression levels and cell apoptosis were analyzed using RT-qPCR, Western blotting or flow cytometry. RESULTS: In C57BL/6 mice, renal IRI induced obvious renal tissue damage, elevation of serum creatinine and blood urea nitrogen levels and renal expression levels of KIM-1, STING, TLR4, P65, NLRP3, caspase-1, caspase-3, Bax, CD68, MPO, IL-1ß, IL-6, and TNF-α, and reduction of Bcl-2 expression level. Treatment of the mouse models with SN-011 for inhibiting STING expression significantly alleviated these changes. In HK-2 cells, H/R exposure caused significant elevation of cellular STING expression and obviously increased cell apoptosis rate, which was significantly lowered by treatment with SN-011. CONCLUSION: Renal STING expression is elevated in mice with renal IRI to exacerbate renal injury by regulating the TLR4/NF-κB/NLRP3 pathway and promoting inflammation and apoptosis in the renal tissues.

Prognostic role of the systemic immune-inflammation index and pan-immune inflammation value for outcomes of breast cancer: a systematic review and meta-analysis.

OBJECTIVE: This review examined the literature for evidence on the prognostic ability of systemic immune-inflammation index (SII) and pan-immune inflammation value (PIV) for predicting overall survival (OS) and disease-free survival (DFS) in breast cancer patients. MATERIALS AND METHODS: PubMed, Embase, Scopus, and Web of Science were searched with Google Scholar for gray literature. All types of studies reporting the association between SII or PIV and OS or DFS of breast cancer were eligible. RESULTS: 13 studies on SII and 4 studies on PIV were included. Meta-analysis showed that a high SII was a significant predictor of OS (HR: 1.97 95% CI: 1.54, 2.52 I2=76%) and DFS (HR: 2.07 95% CI: 1.50, 2.86 I2=79%) in breast cancer patients. These results did not change on sensitivity analysis and were more or less stable on multiple subgroup analyses. Pooled analysis showed that high PIV was also a significant predictor of poor OS (HR: 2.63 95% CI: 1.46, 4.74 I2=71%) and DFS (HR: 1.64 95% CI: 1.23, 2.17 I2=0%) in breast cancer patients. CONCLUSIONS: High SII and PIV can predict poor OS and DFS in breast cancer patients. High heterogeneity and the observational nature of data are important limitations of the review. Further studies are needed specifically on PIV to increase the strength of the evidence.

Aging human abdominal subcutaneous white adipose tissue at single cell resolution.

White adipose tissue (WAT) is a robust energy storage and endocrine organ critical for maintaining metabolic health as we age. Our aim was to identify cell-specific transcriptional aberrations that occur in WAT with aging. We leveraged full-length snRNA-Seq and histology to characterize the cellular landscape of human abdominal subcutaneous WAT in a prospective cohort of 10 younger (≤30 years) and 10 older individuals (≥65 years) balanced for sex and body mass index (BMI). The older group had greater cholesterol, very-low-density lipoprotein, triglycerides, thyroid stimulating hormone, and aspartate transaminase compared to the younger group (p < 0.05). We highlight that aging WAT is associated with adipocyte hypertrophy, increased proportions of lipid-associated macrophages and mast cells, an upregulation of immune responses linked to fibrosis in pre-adipocyte, adipocyte, and vascular populations, and highlight CXCL14 as a biomarker of these processes. We show that older WAT has elevated levels of senescence marker p16 in adipocytes and identify the adipocyte subpopulation driving this senescence profile. We confirm that these transcriptional and phenotypical changes occur without overt fibrosis and in older individuals that have comparable WAT insulin sensitivity to the younger individuals.

[Retrospective study of 70 cases with the head and neck non-parameningeal rhabdomyosarcoma].

Objective: To analyze the treatment outcomes and prognoses of children with head and neck non-parameningeal rhabdomyosarcoma (HNnPM RMS). Methods: A retrospective analysis was performed on the clinical data of children with HNnPM RMS admitted to Beijing Children's Hospital from September 2012 to September 2022. The clinical features, comprehensive treatment modes and prognoses of the patients were analyzed. The overall survival rate (OS) and event free survival rate (EFS) were calculated using the Kaplan-Meier method, and univariate analysis was performed using the Log-rank test. Results: A total of 70 children were included in this study, 38 males and 32 females, with a median age of 47 months (2-210 months). Pathological subtypes including the embryonal in 27 cases, the alveolar in 36 cases and the spindle cell and sclerosing in 7 cases. Thirty children (83.3%) with alveolar type were positive for FOXO1 gene fusion. All 70 children underwent chemotherapy, including 38 with neoadjuvant chemotherapy and 32 with adjuvant chemotherapy. Sixty of 70 children underwent surgery, of whom, 10 underwent two or more surgeries. There were 63 children underwent radiotherapy, including 54 with intensity-modulated radiation therapy, 4 with particle implantation and 5 with proton therapy. The median follow-up was 45 (5-113) months, the 5-year OS was 73.2%, and the 5-year EFS was 57.7%. Univariate analysis showed lymph node metastasis (χ2=5.022, P=0.025), distant metastasis (χ2=8.258, P=0.004), and high Intergroup Rhabdomyosarcoma Study (IRS) group (χ2=9.859, P=0.029) as risk factors for poor prognosis. Before June 2016, the 5-year OS based on BCH-RMS-2006 scheme was 63.6%, and after 2016, the 5-year OS based on CCCG-RMS-2016 scheme was 79.6%. Conclusion: Multidisciplinary combined standardized treatment can offer good treatment outcome and prognosis for children with HNnPM RMS. Local control is a key to the efficacy of comprehensive treatment.

Total mercury in fur, whiskers and whole blood of Caspian seals (Pusa capsica) from north-east of Caspian Sea (Kazakhstan).

Total Mercury (THg) content was determined in the fur of 64 Caspian seals, in the whiskers of 59 individuals and whole blood of 29 individuals. The THg content in Caspian seal fur varied from 258 to 8511 µg/kg, in whiskers from 954 to 12,957 µg/kg, and in whole blood from 88 to 350 µg/l. There were no statistically significant differences in mercury concentration in biomaterial between males and females (Kruskal-Wallis test, p < 0.05). The 1-2-year-old seals contained less mercury compared to older seals. The THg content in Caspian seal samples was comparable to seals from different regions of North Eurasia. Four individuals had mercury concentrations in their fur above the threshold values that can lead to nervous system disorders (>5400 µg/kg).

[Long-term outcome of patients with rectal cancer who achieve complete or near complete clinical responses after neoadjuvant therapy: a multicenter registry study of data from the Chinese Watch and Wait Database].

Objective: To report the long-term outcomes of Chinese rectal cancer patients after adopting a Watch and Wait (W&W) strategy following neoadjuvant therapy (NAT). Methods: This multicenter, cross-sectional study was based on real-world data. The study cohort comprised rectal cancer patients who had achieved complete or near complete clinical responses (cCRs, near-cCRs) after NAT and were thereafter managed by a W&W approach, as well as a few patients who had achieved good responses after NAT and had then undergone local excision for confirmation of pathological complete response. All participants had been followed up for ≥2 years. Patients with distant metastases at baseline or who opted for observation while living with the tumor were excluded. Data of eligible patients were retrospectively collected from the Chinese Wait-and-Watch Data Collaboration Group database. These included baseline characteristics, type of NAT, pre-treatment imaging results, evaluation of post-NAT efficacy, salvage measures, and treatment outcomes. We herein report the long-term outcomes of Chinese rectal cancer patients after NAT and W&W and the differences between the cCR and near-cCR groups. Results: Clinical data of 318 rectal cancer patients who had undergone W&W for over 2 years and been followed up were collected from eight medical centers (Peking University Cancer Hospital, Fudan University Shanghai Cancer Center, Sun Yat-sen University Cancer Center, Shanghai Changhai Hospital, Peking Union Medical College Hospital, Liaoning Cancer Hospital, the First Hospital of Jilin University, and Yunnan Cancer Hospital.) The participants comprised 221 men (69.4%) and 107 women (30.6%) of median age 60 (26-86) years. The median distance between tumor and anal verge was 3.4 (0-10.4) cm. Of these patients, 291 and 27 had achieved cCR or near-cCR, respectively, after NAT. The median duration of follow-up was 48.4 (10.2-110.3) months. The 5-year cumulative overall survival rate was 92.4% (95%CI: 86.8%-95.7%), 5-year cumulative disease-specific survival (CSS) rate 96.6% (95%CI: 92.2%-98.5%), 5-year cumulative organ-preserving disease-free survival rate 86.6% (95%CI: 81.0%-90.7%), and 5-year organ preservation rate 85.3% (95%CI: 80.3%-89.1%). The overall 5-year local recurrence and distant metastasis rates were 18.5% (95%CI: 14.9%-20.8%) and 8.2% (95%CI: 5.4%-12.5%), respectively. Most local recurrences (82.1%, 46/56) occurred within 2 years, and 91.0% (51/56) occurred within 3 years, the median time to recurrence being 11.7 (2.5-66.6) months. Most (91.1%, 51/56) local recurrences occurred within the intestinal lumen. Distant metastases developed in 23 patients; 60.9% (14/23) occurred within 2 years and 73.9% (17/23) within 3 years, the median time to distant metastasis being 21.9 (2.6-90.3) months. Common sites included lung (15/23, 65.2%), liver (6/23, 26.1%), and bone (7/23, 30.4%) The metastases involved single organs in 17 patients and multiple organs in six. There were no significant differences in overall, cumulative disease-specific, or organ-preserving disease-free survival or rate of metastases between the two groups (all P>0.05). The 5-year local recurrence rate was higher in the near-cCR than in the cCR group (41.6% vs. 16.4%, P<0.01), with a lower organ preservation rate (69.2% vs. 88.0%, P<0.001). The success rates of salvage after local recurrence and distant metastasis were 82.1% (46/56) and 13.0% (3/23), respectively. Conclusion: Rectal cancer patients who achieve cCR or near-cCR after NAT and undergo W&W have favorable oncological outcomes and a high rate of organ preservation. Local recurrence and distant metastasis during W&W follow certain patterns, with a relatively high salvage rate for local recurrence. Our findings highlight the importance of close follow-up and timely intervention during the W&W process.

Highest fusion performance without harmful edge energy bursts in tokamak.

The path of tokamak fusion and International thermonuclear experimental reactor (ITER) is maintaining high-performance plasma to produce sufficient fusion power. This effort is hindered by the transient energy burst arising from the instabilities at the boundary of plasmas. Conventional 3D magnetic perturbations used to suppress these instabilities often degrade fusion performance and increase the risk of other instabilities. This study presents an innovative 3D field optimization approach that leverages machine learning and real-time adaptability to overcome these challenges. Implemented in the DIII-D and KSTAR tokamaks, this method has consistently achieved reactor-relevant core confinement and the highest fusion performance without triggering damaging bursts. This is enabled by advances in the physics understanding of self-organized transport in the plasma edge and machine learning techniques to optimize the 3D field spectrum. The success of automated, real-time adaptive control of such complex systems paves the way for maximizing fusion efficiency in ITER and beyond while minimizing damage to device components.