bluuebunny/crossref_metadata_2025 huggingface dataset:
The “blownknee” patient’s stress fracture of distal tibial component after unilateral TKA: A case report
Authors: Sun Quanxiang , Liu Changjie , Sun Xuedong , Liu Zezhong , Liu Xiaoguang , Li Wei , Zhang Yimin
Published: August 2024

Rationale:

Periprosthetic fractures (PPF) are rare complications of total knee arthroplasty (TKA). The most common PPF after TKA is supracondylar femoral fracture, which is a relatively rare complication that is usually associated with high-energy trauma, with a reported incidence ranging from 0.4 to 1.7% according to the AOANJRR. However, in TKA patients, it is rarer that the stress fracture around the tibial prosthesis occurs due to changes in the lower limb force line, increasing weight-bearing, and changes in walking gait.

Patient concerns:

A 68-year-old woman visited our hospital with “both knees had aggravated pain and deformity for 8 years.” TKA was performed first on the left knee and the patient was discharged within 1 week. Three months later, the patient complained of pain in the upper middle 1/3 part of the medial tibia for 2 weeks, which gradually worsened and affected weight-bearing.

Diagnoses:

Physical examination showed that the left knee joint presented varus deformity, and the right valgus deformity, which diagnosed as osteoarthritis of both knees and was so-called “blownknee”. The disease was initially diagnosed as osteoarthritis of both knees on first admission and PPF of the tibia in second.

Interventions:

Three operations were performed on this patient. The first was TKA of the left knee, the second was open reduction and internal fixation of the PPF of the tibia 3 months after the first operation, and the third was TKA of the right knee.

Outcomes:

Until now, the patient has had no recurrent PPF, and the fracture is healing from the last X-ray.

Lessons:

Clinicians should be aware of the possibility of PPF after TKA, especially in such patients, the most preferred surgical treatment method was open reduction and internal fixation of fractures using locking plates, and if the PPF with loosened implants, Revision TKA, or megaprosthesis was the better choice.
Progress, pharmacokinetics and future perspectives of luteolin modulating signaling pathways to exert anticancer effects: A review
Authors: Wang Rui , Li Xia , Xu Yanhan , Li Yangyang , Zhang Weisong , Guo Rongqi , Song Jianxiang
Published: August 2024

Luteolin (3, 4, 5, 7-tetrahydroxyflavone) are natural flavonoids widely found in vegetables, fruits and herbs, with anti-tumor, anti-inflammatory and antioxidant effects, and also play an anti-cancer effect in various cancers such as lung, breast, prostate, and liver cancer, etc. Specifically, the anti-cancer mechanism includes regulation of various signaling pathways to induce apoptosis of tumor cells, inhibition of tumor cell proliferation and metastasis, anti-angiogenesis, regulation of immune function, synergistic anti-cancer drugs and regulation of reactive oxygen species levels of tumor cells. Specific anti-cancer mechanisms include regulation of various signaling pathways to induce apoptosis, inhibition of tumor cell proliferation and metastasis, anti-angiogenesis, reversal of epithelial-mesenchymal transition, regulation of immune function, synergism with anti-cancer drugs and regulation of reactive oxygen species levels in tumor cells. This paper integrates the latest cutting-edge research on luteolin and combines it with the prospect of future clinical applications, aiming to explore the mechanism of luteolin exerting different anticancer effects through the regulation of different signaling pathways, so as to provide a practical theoretical basis for the use of luteolin in clinical treatment and hopefully provide some reference for the future research direction of luteolin.
CONSORT article: Single-cell sequencing analysis revealed CMKLR1+ macrophage as a subpopulation of macrophage with tumor-suppressive characteristics in oral squamous cell carcinoma
Authors: Lou Jiaqi , Luo Guanghui , Zhao Lei , Zhang Huiya
Published: August 2024

Background:

Oral squamous cell carcinoma (OSCC) is an aggressive oral malignancy. Metastasis and postoperative recurrence are major causes of a high mortality of OSCC. The landscape of immune cells in OSCC remained to be comprehensively explored.

Methods:

Tumor tissues of OSCC patients were collected from the Gene Expression Omnibus database, based on which single-cell sequencing analysis was performed to identify subtypes of macrophages and to annotate the subpopulations according to the expression levels of cell marker genes. Functional enrichment analysis was performed to explore the biological processes involved in each cell subcluster. Gene regulatory networks driven by SPECIFIC transcription factors (TFs) were developed applying single-cell regulatory network inference and clustering (SCENIC) analysis. Binding strength between receptors and ligands between different cells was analyzed using cell communication analysis.

Results:

A single-cell landscape in OSCC was successfully developed and a total of 11 cell clusters were identified. Specifically, CD163 + macrophages were a crucial type of macrophage with 4 cell subpopulations, namely, SAT1 + macrophages, IDO1 + macrophages, TRIM29 + macrophages, and CMKLR1 + macrophages. IDO1 + macrophages and CMKLR1 + macrophages mainly had the characteristics of M1-type macrophages. CMKLR1 + macrophages fulfilled the function of M1-type macrophages to inhibit OSCC progression. IDO1 + macrophages and CMKLR1 + macrophages were both involved in the activation response of T cells. CMLKR1 + macrophages had a stronger activating effect on T cells. CMKLR1 + macrophages directly regulated the proliferation of epithelial cells and inhibited the progression of OSCC.

Conclusion:

CMKLR1 + macrophages in OSCC were identified as a crucial cell subpopulation of macrophages in inhibiting tumor progression. Adjusting the infiltration abundance and cell activity of CMKLR1 + macrophages may be a novel therapeutic direction to improve OSCC prognosis.
Association between prediabetes and the incidence of gastric cancer: A meta-analysis
Authors: Wang Shenggang , Zhao Jiamin , Liu Chong
Published: August 2024

Background:

Prediabetes has been found to be associated with an elevated overall risk of cancer, which may be site-specific. we performed a protocol for systematic review and meta-analysis to investigate the correlation between prediabetes and the incidence of gastric cancer (GC).

Methods:

A thorough review of the literature was conducted in the PubMed, Embase, and Web of Science databases to identify pertinent observational studies with longitudinal follow-up. The random-effects model was employed to consolidate the data, taking into account the potential impact of heterogeneity.

Results:

A total of 13 datasets from 8 prospective cohort studies were included. The prevalence of prediabetes was 9.6%. During the mean follow-up duration of 7.1 to 12.2 years, 33,135 patients were diagnosed with GC. According to the results of the pooled analysis, prediabetes was associated with a mildly higher incidence of GC over time (risk ratio: 1.07, 95% confidence interval: 1.01–1.13, P = .03; I
2 = 44%). Subsequent subgroup analyses indicated that the relationship between prediabetes and the heightened risk of GC may not be substantially influenced by factors such as the country in which the study was conducted, the average age of participants, their gender, the definition of prediabetes used, the prevalence of prediabetes at the beginning of the study, the incidence of GC within the studied population, or the adjustment made for body mass index (P for subgroup difference all >.05).

Conclusion:

The presence of prediabetes may increase the risk of GC by a mild amount when compared with people with normoglycemia in community-derived adult populations.
Pressure algometry in the general adult population: Age and sex differences
Authors: Vesal Mina , Roohafza Hamidreza , Feizi Awat , Asgari Karim , Shahoon Hassan , Ani Alireza , Adibi Peyman
Published: August 2024

Experimental pain studies have revealed inter-individual variations in pain perception that are influenced by age, sex, and country of origin. This study aimed to explore the age and sex differences in pressure pain thresholds within the Iranian general population. To assess the pressure pain thresholds, a handheld pressure algometer was applied bilaterally to the middle fingers of both hands. The participants also completed the short form of the McGill Pain Questionnaire to provide a clinical pain rating. This cross-sectional study included 1610 adult subjects (54.96% female, mean age 40.13 ± 10.18 years). The findings indicated that females generally exhibited lower pain thresholds than males when assessing pain detection and tolerance parameters (P < .001). Females also demonstrated a significant lower pressure thresholds and clinical pain ratings compared with men (P < .001). Additionally, significant differences were observed between age groups in terms of pain detection and tolerance thresholds (P = .02 and P = .03, respectively). However, the interaction between sex and age was not significant. No significant differences in pain detection thresholds were observed between the right and left hand (P = .11). This study underscores the potential utility of algometry as a valuable tool for objectifying pain in the Iranian population.
Diagnosis and surgical treatment of obturator hernia in the recent decade with long-term follow-up: A single center experience
Authors: Zhou Bin , Chang Peng , Xu Haibin , Yang Siqi , Xu Hongxing , Shen Danfeng
Published: August 2024

Obturator hernia (OH) is a rare and dangerous disease that can lead to life-threatening consequences, and pelvic computed tomography (CT) is widely used for its diagnosis. There is no consensus regarding the surgical approach and repair methods. Retrospective analysis of the clinical and follow-up data of 15 cases of incarcerated hernias patients admitted to the Department of General Surgery, affiliated to Taicang Affiliated Hospital of Soochow University, from January 2011 to December 2022. OH could be precisely diagnosed with pelvic CT scan, except for occult OH and non-strangulated OH. Thirteen patients underwent emergency surgery, with a total complication rate of 76.9% and no mortality. Ten patients underwent open surgery, and 3 patients underwent laparoscopic surgery, which had advantages in terms of total cost and postoperative hospital stay (P < .05). Emergency patients all underwent simple peritoneal closure, and hernial sac excision was simultaneously performed in 6 of them. A recurrence (7.7%) was detected at 38 months after the first operation. There was no statistically significant difference between the 2 tissue repair methods in terms of recurrent rate. Pelvic CT can be used as a gold standard for the diagnosis of incarcerated OH, but it has limited value in occult OH and non-strangulated OH. Laparoscopic surgery is recommended for patients with a short onset time and no abdominal physical signs. Tissue repair is sufficient for incarcerated OH and hernial sac excision may be unnecessary.
Successful corticosteroid therapy for severe liver injury secondary to herbal traditional Chinese medicine, Mega Defends X, assessed for causality by the updated RUCAM: A case report
Authors: Chai Lu , Wang Ran , Teschke Rolf , Jin Shenghao , Deng Jiao , Qi Xingshun
Published: August 2024

Rationale:

In China, herbal traditional Chinese medicine products are readily obtained without any requirement of prescription and widely used in real life, thereby increasing the incidence of their related herb-induced liver injury (HILI). However, the diagnosis of HILI is still challenging because its clinical manifestations are variable due to lack of any specific biomarkers. Misdiagnosis and inappropriate treatment may result in the progression of HILI.

Patient concerns:

A 55-year-old female patient was admitted to the hospital due to progressive jaundice.

Diagnoses:

The diagnoses of HILI secondary to Mega Defends X, an herbal traditional Chinese medicine product, for which the score was 9 based on the updated Roussel Uclaf Causality Assessment Method of 2016.

Interventions:

The patient received corticosteroid with a stepwise dosage reduction.

Outcomes:

The liver injury significantly improved by corticosteroid treatment.

Lessons:

Corticosteroids should be potentially effective and safe in patients with severe HILI.
Polyarteritis nodosa complicated by renal aneurysm and intestinal perforation: A case report
Authors: Ma Yingying , Luan Luan , Zhang Junjun , Ren Chunfeng , Hou Chunfeng
Published: August 2024

Rationale:

Polyarteritis nodosa (PAN) is a necrotizing vasculitis that affects small- and medium-sized arteries, presenting with diverse clinical manifestations. It can impact tissues and organs throughout the body and may be life-threatening in severe cases. Common causes of death include cardiac, renal, and gastrointestinal complications or aneurysm rupture. While separate reports of renal aneurysm and intestinal perforation exist, the coexistence of these conditions is rarely documented. This study reports a severe case of PAN complicated by both renal aneurysm and intestinal perforation, aiming to deepen the understanding of this disease, aid in clinical diagnosis and treatment, and improve patient prognosis.

Patient concerns:

The patient presented to the hospital with dorsal foot pain and abdominal pain persisting for more than 4 months, along with pain and discomfort in both lower extremities for over 1 month.

Interventions:

The patient was diagnosed with PAN, renal aneurysm, intestinal perforation, and grade 3 hypertension (high risk).

Outcomes:

After treatment, the patient showed normal temperature and blood pressure, relief from abdominal pain, and disappearance of myalgia and numbness in the lower limbs. Additionally, the renal aneurysm shrank significantly, the intestinal perforation healed, the ileostomy was reduced, and the patient’s condition stabilized.

Lessons:

The clinical symptoms of PAN mostly lack specificity, and should be distinguished from microscopic polyangiitis and simulated vasculitis. For patients with intestinal perforation similar to this case, tocilizumab treatment may be effective, but further research is needed to confirm it.
Vascular access device selection
Authors: Nickel Barb
Published: August 2024

A systematic evaluation of vascular access device (VAD) selection incorporates patient, device, and infusate characteristics to ensure optimal device placement. This article explores VAD selection from the perspective of vessel health and preservation and describes VAD selection options and indications, VAD-related complications, and strategies to reduce those complications.
Clinical efficacy of traditional Chinese medicine combined with Western medicine in the treatment of persistent human papillomavirus infection in patients with infertility
Authors: Yang Ling , Zhang Ting , Li Yan , Ma Hong-Long
Published: August 2024

Objective:

To investigate the clinical efficacy of Fuzheng Jiedu formula combined with interferon in the treatment of human papillomavirus (HPV) infection in patients with infertility.

Methods:

A total of 750 infertile patients with persistent HPV infection were randomly divided into Group A (n = 240, interferon), Group B (n = 260, Fuzheng Jiedu formula), and Group C (n = 250, interferon + Fuzheng Jiedu formula). The traditional Chinese medicine (TCM) symptoms, efficacy, immune function, and HPV conversion were compared among the three groups, and statistical analysis was conducted on the data before and after treatment among the three groups, including TCM symptom score, total efficacy, CD3+, CD4+, CD8+, CD4+/CD8+ levels, and HPV-DNA conversion rate.

Results:

The total efficacies of Group A, Group B, and Group C were 89.58%, 62.50%, and 98.00%, respectively; the conversion rates of HPV-DNA in Group A, Group B, and Group C were 62.50%, 67.31%, and 90.00%, respectively. The TCM symptom score of the three groups was most significantly reduced in Group C, followed by Group B, and there was a statistical difference between the groups (P <0.05). The efficacy of the three groups was highest in Group C, followed by Group A, and Group B, with statistical differences (P <0.05). A pairwise comparison of the HPV conversion rates of the three groups showed that Group C had the highest HPV conversion rate (P <0.05); HPV16 and HPV18 subtypes displayed high conversion rates among the different HPV subtypes (P <0.05), whereas the comparisons between the remaining subtypes showed no statistically significant differences (P >0.05). CD3+, CD4+, and CD4+/CD8+ levels showed an increasing trend in the three groups after treatment, whereas the CD8+ level decreased (P <0.05). Pairwise comparison showed that CD3+, CD4+, and CD4+/CD8+ levels were more elevated in Group C than those in Groups A and B (P <0.05).

Conclusion:

Fuzheng Jiedu formula notably improves the efficacy of HPV persistent infection and HPV conversion rate in patients with infertility, and its efficacy is better than that of TCM and Western medicine alone. The mechanism is mainly related to the fact that TCM improves the symptom score of syndromes of spleen asthenia and dampness encumbrance and increases CD3+, CD4+, CD4+/CD8+ levels. The effect of combined therapy on improving immunity is more advantageous than that of TCM or Western medicine alone.
Automated 3D-Body Composition Analysis as a Predictor of Survival in Patients With Idiopathic Pulmonary Fibrosis
Authors: Salhöfer Luca , Bonella Francesco , Meetschen Mathias , Umutlu Lale , Forsting Michael , Schaarschmidt Benedikt Michael , Opitz Marcel Klaus , Kleesiek Jens , Hosch Rene , Koitka Sven , Parmar Vicky , Nensa Felix , Haubold Johannes
Published: August 2024

Purpose:

Idiopathic pulmonary fibrosis (IPF) is the most common interstitial lung disease, with a median survival time of 2 to 5 years. The focus of this study is to establish a novel imaging biomarker.

Materials and Methods:

In this study, 79 patients (19% female) with a median age of 70 years were studied retrospectively. Fully automated body composition analysis (BCA) features (bone, muscle, total adipose tissue, intermuscular, and intramuscular adipose tissue) were combined into Sarcopenia, Fat, and Myosteatosis indices and compared between patients with a survival of more or less than 2 years. In addition, we divided the cohort at the median (high=≥ median, low=<median) of the respective BCA index and tested the impact on the overall survival using the Kaplan-Meier methodology, a log-rank test, and adjusted multivariate Cox-regression analysis.

Results:

A high Sarcopenia and Fat index and low Myosteatosis index were associated with longer median survival (35 vs. 16 mo for high vs. low Sarcopenia index, P=0.066; 44 vs. 14 mo for high vs. low Fat index, P<0.001; and 33 vs. 14 mo for low vs. high Myosteatosis index, P=0.0056) and better 5-year survival rates (34.0% vs. 23.6% for high vs. low Sarcopenia index; 47.3% vs. 9.2% for high vs. low Fat index; and 11.2% vs. 42.7% for high vs. low Myosteatosis index). Adjusted multivariate Cox regression showed a significant impact of the Fat (HR=0.71, P=0.01) and Myosteatosis (HR=1.12, P=0.005) on overall survival.

Conclusion:

The fully automated BCA provides biomarkers with a predictive value for the overall survival in patients with IPF.
CONTINUOUS KIDNEY REPLACEMENT THERAPY DOSAGE AND MORTALITY IN CRITICALLY ILL PATIENTS: A RETROSPECTIVE COHORT STUDY USING MARGINAL STRUCTURAL MODEL
Authors: Faria Maria Luiza Medeiros , Libório Alexandre Braga
Published: August 2024

Background: Continuous kidney replacement therapy (CKRT) is a crucial intervention for hemodynamically unstable patients with acute kidney injury (AKI). Despite the recommendations to offer a CKRT dose of 20 to 25 mL/kg/h, the optimal CKRT dose remains uncertain, especially whether low-dose CKRT is associated with poor outcomes. This study investigated the association between low CKRT dosage and 90-day mortality using a marginal structural model (MSM). Methods: Using the MIMIC-IV database, adult patients who received CKRT for more than 24 h were included. Data on time-fixed and time-dependent variables were collected. Patients were categorized based on CKRT dose thresholds of 13 and 20 mL/kg/h. Results: Among the 1,329 patients, the 90-day mortality rate was 49.6%. The median age of the patients was 62 years (IQR: 52–72). Changes in CKRT dosing during treatment were frequent. Patients with a reduced delivered CKRT dose (<20 and <13 mL/kg/h) generally exhibited low values during the initial days of CKRT, with an increase in the delivered CKRT dose. After adjusting only for baseline variables (traditional Cox regression model), patients receiving CKRT doses <13 mL/kg/h had significantly greater 90-day mortality (HR: 1.70, 95% CI 1.16–2.49) than those receiving CKRT doses ≥13 mL/kg/h. However, after adjusting for time-dependent variables, the CKRT dose was not significantly associated with mortality at either the 13 or 20 mL/kg/h threshold. Additionally, there were no significant associations between the delivered CKRT dose and 90-day mortality within the range of 5 to 40 mL/kg/h. Conclusion: This study highlights the impact of methodological approaches on the association between CKRT dose and mortality and that with personalized adjustments, there may not be a lower limit of the unsafe CKRT dose. However, lower CKRT doses were initially associated with higher mortality, and adjusting for time-dependent variables nullified this association.
Cytoreductive Surgery With Hyperthermic Intraperitoneal Chemotherapy and Liver Resection is a Treatment Option for Patients With Peritoneal and Liver Metastases From Colorectal Cancer
Authors: Dagenborg Vegar Johansen , Brudvik Kristoffer Watten , Lund-Andersen Christin , Torgunrud Annette , Lund-Iversen Marius , Flatmark Kjersti , Larsen Stein Gunnar , Yaqub Sheraz
Published: August 2024

Objective:

To study outcomes after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) in patients also treated for colorectal liver metastases (CLM).

Background:

Colorectal cancer (CRC) frequently metastasizes to the liver and peritoneum and is associated with a poor prognosis. In selected patients, a benefit in overall survival (OS) was shown for both peritoneal metastases (PM-CRC) offered CRS-HIPEC, and CLM treated with surgical resection. However, the presence of CLM was considered a relative contraindication to CRS-HIPEC, causing a paucity of outcome data in this patient group.

Methods:

Patients with PM-CRC having CRS-HIPEC at a single national center between 2007 and 2023, with additional intervention for CLM, were included (previous curative treatment for extraperitoneal and extrahepatic metastases was allowed). Three groups were defined: CLM before CRS-HIPEC (pre-CRS-HIPEC), CLM resected simultaneously with CRS-HIPEC (sim-CRS-HIPEC), and CLM after CRS-HIPEC (post-CRS-HIPEC), aiming to retrospectively analyze outcomes.

Results:

Fifty-seven patients were included and classified as: pre-CRS-HIPEC (n = 11), sim-CRS-HIPEC (n = 29), and post-CRS-HIPEC (n = 17). Median Peritoneal Cancer Index (PCI) was 8; 13 patients had severe complications (Clavien-Dindo ≥3), and no 90-day mortality. Median OS was 48 months after CRS-HIPEC. PCI was a predictor of OS (hazard ratio: 1.11, P < 0.001). We observed no difference in short or long-term outcomes between intervention groups.

Discussion:

This study demonstrated that patients with CLM having CRS-HIPEC had comparable OS to reports on CRS-HIPEC only, likely explained by a low PCI. Simultaneous CLM resection did not increase the risk of severe complications.

Conclusions:

In this national cohort, CRS-HIPEC and CLM intervention offers long-term survival, suggesting that this treatment may be offered to selected patients with PM-CRC and CLM.
Dynamic Assessment of Drain Fluid Amylase Estimates the Risk of CR-POPF Following Pancreatoduodenectomy
Authors: AlMasri Samer , Kim Victoria M. , Hodges Jacob C. , Casciani Fabio , Lee Kenneth K. , Paniccia Alessandro , Vollmer Charles M. , Zureikat Amer H.
Published: August 2024

Objective:

To evaluate whether drain fluid amylase levels on day-1 (DFA1) and day-3 (DFA3) can reliably estimate the risk of clinically relevant-postoperative pancreatic fistula (CR-POPF) following pancreatoduodenectomy (PD) compared to either value alone or in combination with clinicopathologic variables.

Background:

CR-POPF is a major source of morbidity and mortality following PD. Current drain management algorithms are variable and are mostly dependent on DFA1, while the DFA3 is seldom utilized to guide clinical decision making.

Methods:

Between 2015-2020, patients who underwent PD at two high-volume pancreas centers and had intraoperative drain placement with measurement of DFA1 and DFA3 were retrospectively reviewed. Models to predict CR-POPF were constructed using DFA1, DFA3, fistula risk score (FRS) and other patient or treatment-related parameters. The fittest and more parsimonious model was used to construct a CR-POPF risk calculator.

Results:

Nine-hundred-twenty-three patients were included in the analysis. The FRS was high in 100(10.9%), intermediate in 524(57.3%), low in 211(23.1%) and negligible in 79(8.6%) patients. The overall rate of CR-POPF was 9.2%. Five logistic regression models were constructed using variables known to be implicated in CR-POPF. A model based solely on DFA1 and DFA3 with a cross-validated area under the curve of 0.846 was selected. A calculator using DFA1 and DFA3 was created based on this model to estimate the risk of CR-POPF.

Conclusions:

Risk of CR-POPF following pancreatoduodenectomy can be accurately estimated based on measurement of DFA1 and DFA3. Our CR-POPF kinetics calculator can facilitate postoperative risk stratification and guide drain management algorithms
Impact of Infrared Indocyanine Green Fluorescence Imaging-guided Laparoscopic Hepatectomy on Securing the Resection Margin for Colorectal Liver Metastasis
Authors: Kato Toru , Imamura Masafumi , Kyuno Daisuke , Kimura Yasutoshi , Kukita Kazuharu , Murakami Takeshi , Yoshida Eiji , Mizuguchi Toru , Takemasa Ichiro
Published: August 2024

Background:

Laparoscopic hepatectomy for colorectal liver metastases (CRLM) is performed worldwide. However, owing to a lack of palpatory information and difficulties associated with accurate intraoperative ultrasonographic diagnosis, the tumor may be exposed at the hepatic transection margin. This study aimed to investigate the pathological significance of near-infrared (NIR) fluorescence imaging with indocyanine green (ICG)-guided laparoscopic hepatectomy and determine its usefulness in securing the resection margin for CRLMs.

Methods:

Fifty-nine patients who underwent laparoscopic hepatectomy for CRLM using NIR fluorescence imaging between February 2017 and June 2021 at Sapporo Medical University Hospital were included. Generally, all patients received intravenous ICG (2.5 mg/body) as a fluorescence agent 1 to 2 days before surgery. During the surgical procedure, real-time NIR fluorescence imaging was repeatedly performed to assess the surgical margins.

Results:

Of the 94 tumors in 59 patients, laparoscopic NIR fluorescence imaging identified 56 tumors (59.6%) on the liver surface. Pathological analysis indicated clear margins in 96.6% (57/59) of patients. Examination of paraffin-embedded sections, which were successful in only 20 of 94 cases (21.3%), revealed that there were no tumor cells positive for NIR fluorescence, and the median distance of the continuous fluorescent signal from the tumor margin was 1.074 mm.

Conclusions:

We demonstrated a high R0 rate using NIR fluorescence-guided hepatectomy. This technique has the potential to improve intraoperative tumor identification and tumor margin assurance and reduce the rate of positive resection margins in patients with CRLMs.
Cyclic Alternating EEG Patterns: From Sleep to Encephalopathy
Authors: Misirocchi Francesco , Mutti Carlotta , Hirsch Lawrence J. , Parrino Liborio , Florindo Irene
Published: August 2024

In the 2021 version of the Standardized Critical Care EEG Terminology, the American Clinical Neurophysiology Society introduced new definitions, including for the cyclic alternating pattern of encephalopathy (CAPE). CAPE refers to changes in background EEG activity, with two patterns alternating spontaneously in a regular manner. CAPE shares remarkable similarities with the cyclic alternating pattern, a natural EEG phenomenon occurring in normal non–rapid eye movement sleep, considered the main electrophysiological biomarker of sleep instability. This review explores similarities and differences between cyclic alternating pattern and CAPE and, leveraging the existing expertise on cyclic alternating pattern, aims to extend knowledge on CAPE. A standardized assessment of CAPE features is key to ascertain its prevalence and clinical significance among critically ill patients and to encompass the impact of confounding factors such as anesthetic and sedative agents. Although the preservation of non–rapid eye movement sleep-related elements has a well-known prognostic value in the critical care setting, the clinical importance of cyclic oscillating patterns and the prognostic significance of CAPE remain to be elucidated.
Electroconvulsive Therapy in a Patient With Cerebral Aneurysm, Normal Pressure Hydrocephalus With Ventriculoperitoneal Shunt, and Severe Acquired Pyloric Stenosis
Authors: Jacob Titus , Grözinger Michael , Papenfuß Tim , Mai Matthias , Gahr Maximilian
Published: August 2024

Cerebral aneurysm (CA), normal pressure hydrocephalus (NPH) with ventriculoperitoneal shunt (VPS), and pyloric stenosis increase the risk of complications related to electroconvulsive therapy (ECT). Whereas there is some evidence for the safety of ECT in patients with CA and NPH with VPS, there is none in patients with pyloric stenosis that increases the risk of aspiration during short anesthesia. A 67-year-old female patient with a small and stable aneurysm of the right anterior cerebral artery, NPH with VPS, and severe pyloric stenosis (as a result of suicidal ingestion of pipe cleaner) suffering from therapy-resistant depression and chronic suicidal tendencies was treated successfully with 15 sessions of ECT. The following measures were taken to increase ECT-related safety and may help physicians in their decision-making process in similar cases: careful risk assessment based on presentation and discussion of the case in an academic multidisciplinary neurovascular team, glycerol trinitrate sublingual spray before short anesthesia and (after development of hypotension) switching to a pro re nata (PRN) medication with urapidil directly after electric stimulation in case of a relevant increase in blood pressure, examination of the VPS after five stimulations, oral administration of 30 mL of sodium citrate (0.3 molar) before ECT to increase the gastric pH, and establishment of a specific diet and fasting plan (generally only liquid oral food, discontinuation of oral food intake 20 hours, and administration of water only 14 hours before ECT).
Controlling a new plasma regime
Authors: Lennholm M. , Aleiferis S. , Bakes S. , Bardsley O. P. , van Berkel M. , Casson F. J. , Chaudry F. , Conway N. J. , Hender T. C. , Henderson S. S. , Kool B. , Lafferty M. , Meyer H. F. , Mitchell J. , Mitra A. , Osawa R. , Otin R. , Parrot A. , Thompson T. , Xia G. , the STEP Team
Published: August 2024

Success of the UK’s Spherical Tokamak for Energy Production (STEP) programme requires a robust plasma control system. This system has to guide the plasma from initiation to the burning phase, maintain it there, produce the desired fusion power for the desired duration and then terminate the plasma safely. This has to be done in a challenging environment with limited sensors and without overloading plasma-facing components. The plasma parameters and the operational regime in the STEP prototype will be very different from tokamaks, which are presently in operation. During fusion burn, the plasma regime in STEP will be self-organizing, adding further complications to the plasma control system design. This article describes the work to date on the design of individual controllers for plasma shape and position, magneto hydrodynamic instabilities, heat load and fusion power. Having studied ‘normal’ operation, the article discusses the philosophy of how the system will handle exceptions, when things do not go exactly as planned.

This article is part of the theme issue ‘Delivering Fusion Energy – The Spherical Tokamak for Energy Production (STEP)’.
Staying positive: producing net power
Authors: Acres Jack , Antoniou Ioannis , Christie Finlay , Blackburn Daniel , Knight Samuel
Published: August 2024

The Spherical Tokamak for Energy Production (STEP) prototype powerplant (SPP) will be a first-of-a-kind powerplant—its prime objective is to export electrical power, to the national power transmission system (‘grid’), above 100 MWe. As part of a wider issue, addressing the STEP concept design, this article seeks to explore how electrical power will be generated from a spherical tokamak heat source. Accordingly, the following key functions of the SPP power infrastructure are reviewed.

Cooling the tokamak
: cooling the tokamak while extracting useful thermal energy.

Generating power
: conversion of thermal energy to electrical energy (power generation).

Managing energy
: management of the site-wide distribution, storage and energy export.

In each of these areas, the design scope, challenges and solution spaces have been discussed. This has shaped the design of the SPP power infrastructure, which in turn has ensured a powerplant design focused on operability and performance. Furthermore, it has been demonstrated that the SPP will achieve its prime objective in generating net power, which is enabled by a unique power infrastructure. Confidence in the ability to generate net power will be refined as the design matures. Finally, this article recommends key opportunities that STEP could use to improve power generation and reduce the parasitic load of the SPP.

This article is part of the theme issue ‘Delivering Fusion Energy – The Spherical Tokamak for Energy Production (STEP)’.
Fusing together an outline design for sustained fuelling and tritium self-sufficiency
Authors: Lord Michael , Bennett Iryna , Harrington Chris , Cooper Adam , Lee-Lane Dan , Cureton Adam , Olde Cameron , Thompson Megan , Jayasundara Dinusha , Meatyard Toby
Published: August 2024

Ensuring tritium fuel self-sufficiency while maintaining continuous and high-specification fuel flow to the tokamak via a low tritium inventory and controllable fuel cycle is a significant challenge to the STEP plant design. Effective and high-quality fuelling and exhaust design is required to sustain and control a stable plasma, whereas fuel sufficiency is required to prevent depletion of available tritium supply. Concerns regarding the lack of tritium availability preventing continuous tritium import are countered by breeding, where highly energetic neutrons from the core fusion reactions interact with lithium atoms suspended in the surrounding breeder blanket to produce tritium. The compact nature of STEP prohibits the integration of inboard breeder blankets posing a significant challenge for the design team looking to ensure more tritium is bred and made available than consumed within the core plasma. This paper outlines how purposeful technology selection and system architecting has converged on the outline of a conceivable and tritium-capable fuel cycle and breeder blanket design. Before introducing the STEP fuel cycle design outline and summarizing the approach undertaken to address the challenges facing plasma fuelling, key aspects of fuel self-sufficiency are discussed. This includes discussing a proposed helium-cooled liquid lithium breeder blanket and possible technology options for tritium extraction from lithium. Lastly, there is a brief process modelling overview, which emphasizes the central contribution of various employed modelling methods. Reflections on the presented fuel cycle design outline conclude that substantial development work is still required to realize a continuous tritium fuel cycle design and overcome the major challenges posed by tritium and lithium handling. Reflections on the presented breeder blanket design proposal conclude that while many substantial risks and blockers remain to achieve fuel self-sufficiency, high breeding ratios are expected to be achievable with a compact spherical tokamak configuration. Nonetheless, it is recognized that further consideration is required to ensure that the selection of liquid lithium as a breeder medium provides the overall simplest route to a self-sufficient and realizable design.

This article is part of the theme issue ‘Delivering Fusion Energy – The Spherical Tokamak for Energy Production (STEP)’
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Impacts of Disinfection Methods in a Granular Activated Carbon (GAC) Treatment System on Disinfected Drinking Water Toxicity and Antibiotic Resistance Induction Potential
Authors: Feng Yinmei , Lau Stephanie S. , Mitch William A. , Russell Caroline , Pope Greg , Gu April Z.
Published: August 2024

Abstract Figure

Graphic Abstract

Granular activated carbon (GAC) treatment followed by chlorination (GAC/Cl2) and chlorination followed by chloramination (Cl2/NH2Cl) are two methods utilized by drinking water treatment facilities to mitigate the formation of disinfection byproducts (DBPs) in treated water. However, the effectiveness of these methods in reducing the overall toxicity of drinking water, driven by DBPs, remains largely unknown. In this study, we evaluate the total toxicity of water samples from a pilot-scale GAC system with post-chlorination (GAC/Cl2), and occasionally pre-chlorination upstream of GAC (Cl2/GAC/Cl2), compared to water treated by chlorination followed by chloramination (Cl2/NH2Cl). The research was conducted at various bromide and iodide levels and across three GAC bed volumes. To assess DNA stress and oxidative stress in water extracts, we employed the yeast toxicogenomic assay and human cell RT-qPCR assay, along with the DBP analysis from our previous study. Our results indicated that under environmental halogen conditions, GAC/Cl2typically reduces both genotoxicity and oxidative stress in treated water more effectively than Cl2/NH2Cl and Cl2treatment. However, Cl2/GAC/Cl2does not consistently lower toxicity compared to GAC/Cl2. Notably, under high halogen conditions, Cl2/GAC/Cl2fails to reduce genotoxicity and oxidative stress compared to samples without GAC treatment. Correlation analysis suggested that iodinated DBPs (I-DBPs) and nitrogenous DBPs (N-DBPs) were particularly associated with increased DNA stress and oxidative stress, indicating these classes of DBPs as significant contributors to the observed toxicity. While neither of these two categories of DBPs are regulated by the EPA, it appears that unregulated and unidentified DBPs significantly contribute to the genotoxicity and oxidative stress in drinking water. This research highlights the complex dynamics of water treatment processes and underscores the critical impact of unregulated DBPs on water toxicity.
Nonlinear thinking in ecology and evolution: The case for ecological scaling of the Threshold Elemental Ratio
Authors: Tumolo Benjamin B. , Olson Carly R. , Larson Erin I. , Halvorson Halvor M. , Wagner Catherine E. , Krist Amy C. , Osburn Felicia S. , Moody Eric K. , Rock Linnea A. , Ogbenna Uchechukwu V. C. , Wess Eli N. , Najev Briante , Pignatelli Anthony J. , Corman Jessica R.
Published: August 2024

Nonlinear dynamics govern ecological processes, thus understanding thresholds is important for measuring and forecasting effects of climate change and management of natural resources. However, identifying whether and how such thresholds scale across biological levels of organization remains challenging. Ecological stoichiometry, the study of the balance of multiple elements and energy in ecological systems, provides a framework for scaling thresholds. We broaden a key organismal concept from ecological stoichiometry theory, the Threshold Elemental Ratio (TER), to study how nonlinear dynamics operate in evolutionary and ecological processes across the organizational hierarchy. Traditionally, TERs are used to describe the elemental ratio at which the limitation of organismal growth shifts from one element to another. Following this definition, we make a case for broadening the ecological scale of the TER beyond organisms to include populations, clades, communities, and ecosystems. We show how TERs can be detected and translated across different scales of biological and evolutionary organization through simulation modeling, literature review, and synthesis of empirical examples from diverse systems and ecological scales including: cyanotoxin production in lakes, alder-salmon dynamics, and the Cambrian explosion. Collectively, we demonstrate that TERs are widespread and consequential across levels of biological organization and that such thresholds manifest from a diversity of mechanisms. Thus, scaling of the TER concept holds promise for advancing our understanding of nonlinear dynamics from the micro-evolutionary to macro-ecological.
Neural dynamics of visual streams interactions during memory-guided actions investigated by intracranial EEG
Authors: Moraresku Sofiia , Hammer Jiri , Dimakopoulos Vasileios , Kajsova Michaela , Janca Radek , Jezdik Petr , Kalina Adam , Marusic Petr , Vlcek Kamil
Published: August 2024

The dorsal and ventral visual streams play distinct roles in visual processing for action: the dorsal stream is assumed to support real-time actions, while the ventral stream facilitates memory-guided actions. As the recent evidence suggests a more integrated function of these streams, we investigated the neural dynamics and functional connectivity between them during memory-guided actions using intracranial EEG. We tracked neural activity in the inferior parietal lobule in the dorsal stream, and ventral temporal cortex in the ventral stream as well as hippocampus during a delayed action task. We found increased alpha power in both streams during the delay, indicating their role in maintaining visual information. We also observed an increase in theta band synchronization between the inferior parietal lobule and ventral temporal cortex, and between the inferior parietal lobule and hippocampus during the delay. Our study provides unique electrophysiological evidence for close interactions between dorsal and ventral streams, supporting an integrated processing model.
Reliability of tactile perception and suppression measurements
Authors: Voudouris Dimitris , Georgiadis Petros , Fiehler Katja , Arikan Belkis Ezgi
Published: August 2024

Tactile signals arising on one’s own body allow estimation of one’s own sensory state and foster interactions with the environment. However, tactile perception can be influenced by various factors. For instance, tactile perception is suppressed on a moving limb compared to when it is resting, a phenomenon termed tactile suppression. Here we examine whether tactile perception during resting and during movement is robust over shorter and longer time intervals. Participants had to detect tactile stimuli of various intensities on their index finger while this finger was resting or moving (finger extension). This detection task was performed on four sessions at separate days across a period of one month. We found that tactile perception during resting is robust within single sessions and across days. However, tactile perception during movement changed across days, but these changes lacked a clear systematic pattern. We further show that temporal changes in perception alone cannot fully account for the previously reported tactile suppression effects. Finally, split-half correlations reveal high consistency in the estimated perceptual measures, demonstrating that estimates of tactile perception are robust across measurement points.
CryptoBench: Cryptic protein-ligand binding sites dataset and benchmark
Authors: Škrhák Vít , Novotný Marian , Feidakis Christos P. , Krivák Radoslav , Hoksza David
Published: August 2024

Structure-based methods for detecting protein-ligand binding sites play a crucial role in various domains, from fundamental research to biomedical applications. However, current prediction methodologies often rely on holo (ligand-bound) protein conformations for training and evaluation, overlooking the significance of the apo (ligand-free) states. This oversight is particularly problematic in the case of cryptic binding sites (CBSs) where holo-based assessment yields unrealistic performance expectations. To advance the development in this domain, we introduce CryptoBench, a benchmark dataset tailored for training and evaluating novel CBS prediction methodologies. CryptoBench is constructed upon a large collection of apo-holo protein pairs, grouped by UniProtID, clustered by sequence identity, and filtered to contain only structures with substantial structural change in the binding site. CryptoBench comprises 1,107 structures with predefined cross-validation splits, making it the most extensive CBS dataset to date. To establish a performance baseline, we measured the predictive power of sequence- and structure-based CBS residue prediction methods using the benchmark. We selected PocketMiner as the state-of-the-art representative of the structure-based methods for CBS detection, and P2Rank, a widely-used structure-based method for general binding site prediction that is not specifically tailored for cryptic sites. For sequence-based approaches, we trained a neural network to classify binding residues using protein language model embeddings. Our sequence-based approach outperformed PocketMiner and P2Rank across key metrics, including AUC, AUPRC, MCC, and F1 scores. These results provide baseline benchmark results for future CBS and potentially also non-CBS prediction endeavors, leveraging CryptoBench as the foundational platform for further advancements in the field.
Exogenous ECM in an environmentally-mediatedin vitromodel for cardiac fibrosis
Authors: Pachter Natalie , Allen Kristen , Hookway Tracy A
Published: August 2024

Few clinical solutions exist for cardiac fibrosis, creating the need for a tunablein vitromodel to better understand fibrotic disease mechanisms and screen potential therapeutic compounds. Here, we combined cardiomyocytes, cardiac fibroblasts, and exogenous extracellular matrix (ECM) proteins to create an environmentally-mediatedin vitrocardiac fibrosis model. Cells and ECM were combined into 2 types of cardiac tissues-aggregates and tissue rings. The addition of collagen I had a drastic negative impact on aggregate formation, but ring formation was not as drastically affected. In both tissue types, collagen and other ECM did not severely affect contractile function. Histological analysis showed direct incorporation of collagen into tissues, indicating that we can directly modulate the cells’ ECM environment. This modulation affects tissue formation and distribution of cells, indicating that this model provides a useful platform for understanding how cells respond to changes in their extracellular environment and for potential therapeutic screening.