bluuebunny/crossref_metadata_2025 huggingface dataset:
Coronal tibiofemoral subluxation in patients with osteoarthritis was corrected after total knee arthroplasty
Authors: Li Ruibo , Fu Peng
Published: September 2022

The objective of this study was to investigate the effect of preoperative coronal tibiofemoral subluxation (CTFS) on postoperative mechanical alignment in patients undergoing total knee arthroplasty (TKA) for primary knee osteoarthritis (OA) and to investigate whether TKA can correct preoperative CTFS. We hypothesized that TKA would correct CTFS in patients with knee OA. A retrospective analysis of 102 patients with knee OA who underwent TKA was performed. The preoperative and postoperative CTFS and mechanical alignment were measured and compared. At the same time, the baseline values of CTFS and mechanical alignment in “normal” patients were measured and compared with those in the operation group. Eighty patients were eventually enrolled in the study. Mechanical alignment was corrected from 7.3 ± 5.2°, preoperatively, to 1.6 ± 2.3° postoperatively, while the tibiofemoral subluxation was corrected from 5.3 ± 2.6 mm, preoperatively, to 2.3 ± 2.7 mm postoperatively. There was no significant correlation between preoperative CTFS and gender (r = 0.03), BMI (r = −0.09), age (r = 0.05), or preoperative mechanical alignment (r = 0.09). In addition, there was no correlation between the degree of correction of CTFS and the degree of correction of overall mechanical alignment (r = 0.14). The difference between the value for CTFS in the “normal” patients and the preoperative value for arthritis cohorts were statistically significant (P = .004). However, no significant difference was appreciated between the value for CTFS in the “normal” patients and the postoperative value for TKA cohorts (P = .25). Preoperative CTFS does not affect postoperative mechanical alignment. Excellent TKA can correct preoperative CTFS in OA patients to reduce prosthesis wear and improve postoperative patient satisfaction.
HER2 protein expression correlates with Lauren classification and P53 in gastric cancer patients
Authors: Chu Yiming , Li Hongbo , Wu Dan , Guo Qingqu
Published: September 2022

Human epidermal growth factor receptor 2 (HER2) is a key pathological characteristic of gastric cancer (GC). However, the clinical significance of HER2 expression in gastric carcinoma remains controversial. The purpose of this study was to analyze the clinicopathological characteristics of HER2 protein expression, Lauren classification and tumor protein p53 (P53) expression and to evaluate the clinical significance of HER2 protein expression. A total of 176 consecutive patients were prospectively recruited between January 2014 and December 2016 at the Second Affiliated Hospital of Zhejiang University School of Medicine. Histological analysis of the resected tissue was performed for HER2 protein expression using immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH). Additionally, the expression status of HER2 protein and clinicopathological features were analyzed using the chi-squared (χ
2) test. Survival analysis was performed using the Kaplan–Meier method, and differences between the survival curves were determined using the log-rank test. All statistical analyses were conducted using SPSS 22.0 statistical software program (IBM Corp., Armonk, NY). A total of 176 patients with GC were enrolled in this study. Intratumoral heterogeneity of HER2 protein overexpression was observed in 42 of 176 cases with IHC grade 2+, accompanied by FISH positivity and IHC grade 3+. HER2 protein expression was correlated with tumor differentiation (P < .001), Lauren classification (P = .001), Borrmann type (P = .003) and P53 expression (P < .001). HER2 protein positivity was associated with significantly higher overall survival (OS) (P = .038). Overexpression of HER2 protein was observed in 23.9% of the cases and was significantly related to the Lauren intestinal subtype and P53 negative expression. HER2 protein overexpression was independently associated with higher OS.
Effects of the nurse-led program on disabilities improvement in patients with ischemic stroke
Authors: Wang Suping , You Jingyan , Lin Jing , Fu Xiumei , Ning Min , Mo Yuzhu , Yang Shoujiao
Published: September 2022

To evaluate whether the nurse-led program can improve disabilities in patients with ischemic stroke for more than 6 months. This is a randomized, open-label study. Participants in the usual-care group received the usual care that included verbal stroke-related education and secondary prevention. Participants in the active group received the usual care plus the nurse-led program intervention. The disability was evaluated using National Institutes of Health Stroke Scale (NIHSS). The Mental Health Inventory-5 (MHI-5) was used to assess mental health status (MHS). The median duration since ischemic stroke was 8.4 and 8.6 months, respectively. At baseline, there was no difference in the median NIHSS value and the NIHSS category between these 2 groups. After 6 months’ follow-up, the median NIHSS value was lower in the active group (4.1 vs 6.3). The proportion of patients with NIHSS of 1 to 4 was higher (50.0% vs 28.6%) while the proportion of patients with NIHSS of 5 to 12 (24.1% vs 51.8%) was lower in the active group. After multivariate regression analysis, the nurse-led program was negatively associated with increased NIHSS category (odds ratio of 0.70 and 95% confidence interval of 0.62–0.88). In the group with MHI-5 less than median, the nurse-led program was not associated with NIHSS category. While in the group with MHI-5 greater than median, the nurse-led program was associated decreased NIHSS category, with a significant interaction (P value = .03). In ischemic stroke patients for more than 6 months, the nurse-led program improves disabilities, which might be related to MHS improvement.
Clinical analysis and literature review of a case of ovarian clear cell carcinoma with PIK3CA gene mutation: A case report
Authors: Farah Abdulkarim Mohamed , Gu Shiyu , Jia Yan
Published: September 2022

Rationale:

Ovarian clear cell carcinoma (OCCC) is an uncommon malignant form of 5 subtypes of ovarian cancer, accounting for approximately 5% to 25% of all ovarian cancers. OCCC is usually diagnosed at a young age and an early stage. More than 50% of patients are associated with endometriosis. It shows less sensitivity to platinum-based chemotherapies, high recurrence, and poor prognosis, especially late. However, platinum-based chemotherapies remain the first-line treatment. Meanwhile, new treatment modalities have been explored, including immune checkpoint inhibitors and PI3K-AKT-mTOR pathway inhibitors.

Patient concern:

A 48-year-old Chinese woman, Gravida2 Para1, complained of irregular and painful vaginal bleeding for 4 months.

Diagnosis:

The patient was diagnosed with stage IC ovarian clear cell carcinoma that presented with a mutation of the phosphatidylinositol 4,5-bisphosphate 3-kinase alpha subunit (PIK3CA) gene.

Intervention:

We performed an early diagnosis and complete surgical resection of the tumor with platinum-based chemotherapy.

Outcome:

This patient with mutation of the PIK3CA gene was sensitive to platinum-based chemotherapy, showed a significant downwards trend in tumor markers, and was in good health within the year of follow-up.

Lessons:

This study described an OCCC case that presented with a PIK3CA mutation and was successfully managed with careful and complete resection of the tumor. This patient with mutation of the PIK3CA gene was sensitive to platinum-based chemotherapy, showed a significant downwards trend in tumor markers, and did not have recurrence after a year of follow-up, indicating a reasonably good prognosis. Therefore, surgery plus platinum drug chemotherapy is still the best strategy for OCCC treatment. In addition, it is recommended for such patients to undergo genetic testing as much as possible to predict the clinical treatment effect.
Radiographic assessment of root canal morphology of mandibular central incisors using new classification system: A cross-sectional study
Authors: Alobaid Mohammed A. , Alshahrani Ebtihal M. , Alshehri Ebtsam M. , Shaiban Amal S. , Haralur Satheesh B. , Chaturvedi Saurabh , Khaled Addas Mohamed
Published: September 2022

Lack of basic knowledge about the external and internal anatomies of the root canal system and common variations in teeth may lead to various procedural errors or treatment failure. In this study, the root canal configurations of mandibular incisors and the symmetry of the contralateral incisors of Saudi Arabian subpopulations were analyzed and determined using cone beam computed tomography (CBCT). A retrospective evaluation of 700 patients was conducted, and 1260 fully developed permanent mandibular central incisors were assessed. The number of root canals was determined, and the internal root canal anatomies were categorized based on Ahmed et al.’s criteria. The CBCT images were independently evaluated by 2 trained dentists and an endodontist. The data were assessed using the chi-square and one-way analysis of variance tests. All the mandibular central incisors included in the study were single-rooted. According to Ahmed et al’s classification system, the most common classification (82.6%) was 1ManA1 (Vertucci type I), followed by 1ManA1-2-1 (Vertucci type III; 13%). Second canals were more frequently recorded in the male participants than in the female participants. The root canal configuration between contralateral incisors was largely symmetrical. Most of the mandibular incisors in the examined Saudi Arabian population had a single canal. Nevertheless, a substantial number of patients had a complex root morphology. Hence, CBCT can be utilized as a potential supplementary tool during root canal treatment.
Diagnostic value of carcinoembryonic antigen combined with cytokines in serum of patients with colorectal cancer
Authors: Ma Yunfeng , Zhang Ya , Bi Yu , He Longmei , Li Dandan , Wang Dan , Wang Mengying , Wang Xiaoqin
Published: September 2022

In clinical practice, colorectal cancer (CRC) is difficult to distinguish from ulcerative colitis and colon polyps. Practical markers are useful for diagnosing and treating patients with CRC. Carcinoembryonic antigen (CEA) is a biomarker for diagnosing patients with CRC. However, the diagnostic sensitivity and specificity of CEA are not high. Interleukin (IL)-10, IL-17A, tumor necrosis factor-alpha (TNF-α), interferon-gamma (IFN-γ), and transforming growth factor beta (TGF-β) are assumed to be closely related to the occurrence and development of human cancer. Some have been used as diagnostic markers in CRC. It remains unclear whether cytokines in combination with CEA could be used as biomarkers for the diagnosis of CRC. Serum levels of IL-10, IL-17, TNF-α, IFN-γ, and TGF-β in patients with CRC, ulcerative colitis, colonic polyps, stomach cancer, and healthy controls were measured by enzyme-linked immunosorbent assay. The serum level of CEA was detected using electrochemiluminescence. The value of the cytokines combined with CEA as a biomarker panel for the diagnosis of CRC was assessed. CEA, IL-10, IL-17A, TNF-α, and TGF-β levels were significantly increased in CRC. CEA displayed a higher specificity than the other cytokines. IL-17A, TNF-α, and TGF-β displayed higher sensitivities than CEA, IL-10, and IFN-γ in the diagnosis of CRC. The combination of serum CEA, IL-17A, and TNF-α achieved higher diagnostic efficacy for CRC (area under the curve = 0.935). The combination of CEA, IL-17, and TNF-α has better diagnostic efficacy than CEA alone in CRC. A panel containing IL-17A, TNF-α, and CEA could be a promising molecular biomarker panel to diagnostically differentiate CRC from ulcerative colitis, colon polyps, and stomach cancer.
Response to [177Lu]Lu-PSMA radioligand therapy in metastatic castration-resistant prostate cancer patients presenting with only lymph node metastases
Authors: Zisser Lucia , Yu Josef , Oszwald André , Wollenweber Tim , Kretschmer-Chott Elisabeth , Grubmüller Bernhard , Kramer Gero , Shariat Shahrokh F. , Mitterhauser Markus , Vraka Chrysoula , Hacker Marcus , Haug Alexander R. , Rasul Sazan
Published: September 2022

Objective

[177Lu]Lu-PSMA radioligand therapy (PSMA-RLT) is a promising therapy for patients with metastatic castration-resistant prostate cancer (mCRPC) and offers a survival benefit particularly to patients with only lymph node metastases. We therefore sought to evaluate the clinical outcome of this therapy in such a cohort.

Methods

Of all prostate cancer patients admitted to our department between September 2015 and March 2019 to receive 1–4 courses of PSMA-RLT (each course consisted of three cycles of highly standardized PSMA-RLT every 4 weeks), only 10 consecutive men were found to have nodal metastases only and were analyzed retrospectively.

Results

Nine out of 10 patients responded to their first PSMA-RLT course with a mean prostate-specific antigen (PSA) decline of 71.8 ± 25.2%, seven of them demonstrated a PSA decline of ≥50%. Collectively, seven of eight patients responded to further PSMA-RLT courses with a total PSA reduction of 59.8 ± 30.0%, five of which showed a PSA reduction of ≥50%. One patient experienced complete remission. Median progression-free survival was 85 weeks (range 14–255 weeks) and median overall survival was not reached during the median observation time of 209 weeks (30–298 weeks). Univariate Cox-regression identified initial PSA decline as the only predictive parameter for progression-free survival (P = 0.047).

Conclusion

mCRPC patients with only lymph node metastases showed favorable survival and excellent response to PSMA-RLT, leading to transient partial remission of the disease in most of them.
Tofacitinib Salvage Therapy for Children Hospitalized for Corticosteroid- and Biologic-Refractory Ulcerative Colitis
Authors: Constant Brad D. , Baldassano Robert , Kirsch Jacqueline , Mitchel Elana B. , Stein Ronen , Albenberg Lindsey
Published: September 2022

Objectives:

Colectomy rates following acute severe ulcerative colitis have plateaued around 20% despite intravenous corticosteroid and intensified anti-tumor necrosis factor (TNF) biologic dosing. Recent studies have shown tofacitinib to provide additional benefit in further decreasing colectomy rates among hospitalized adult patients with corticosteroid- and anti-TNF-nonresponsive ulcerative colitis. Pediatric data describing the effectiveness of tofacitinib for this indication does not yet exist. We aimed to describe the treatment courses and colectomy-free survival among pediatric patients treated with tofacitinib while hospitalized for refractory ulcerative colitis.

Methods:

We performed a retrospective single-center cohort study of consecutive hospitalized pediatric patients initiating tofacitinib for refractory ulcerative colitis from 2018 to 2021. The primary outcome was 90-day colectomy-free survival. Secondary outcomes included colectomy-free clinical remission, corticosteroid independence, colectomy-free tofacitinib drug-persistence, tofacitinib-related adverse events, and postoperative complications. Baseline characteristics and details of the timing and positioning of therapies utilized during hospitalization were described. Outcomes were described using counts, percentages, and Kaplan-Meier curves.

Results:

Eleven patients met inclusion criteria. All patients demonstrated nonresponse to both intravenous corticosteroids and anti-TNF therapy prior to tofacitinib initiation. Median hospitalization length was 22 days and mean maximum pediatric ulcerative colitis activity index during hospitalization was 68. Eight of 11 patients remained colectomy-free at 90 days following hospital admission and 6 remained colectomy-free over median 182-day follow-up, including 4 of whom remained on tofacitinib.

Conclusions:

Tofacitinib may represent a new treatment option for hospitalized pediatric patients with corticosteroid- and anti-TNF-nonresponsive ulcerative colitis. Future research is essential in determining the optimal positioning of these therapies.
Symptom Burden and Quality of Life With Chemotherapy for Recurrent Ovarian Cancer: The Gynecologic Cancer InterGroup-Symptom Benefit Study
Authors: Lee Yeh Chen , King Madeleine T. , O'Connell Rachel L. , Lanceley Anne , Joly Florence , Hilpert Felix , Davis Alison , Roncolato Felicia T. , Okamoto Aikou , Bryce Jane , Donnellan Paul , Oza Amit M. , Avall-Lundqvist Elisabeth , Berek Jonathan S. , Ledermann Jonathan A. , Berton Dominique , Sehouli Jalid , Feeney Amanda , Kaminsky Marie-Christine , Diamante Katrina , Stockler Martin R. , Friedlander Michael L. ,   for the GCIG Symptom Benefit Group
Published: September 2022

(Abstracted from Int J Gynecol Cancer 2022;32:761–768)

Patients with recurrent ovarian cancer often experience a multitude of symptoms related to disease progression and the cumulative toxicities from multiple treatment regimens. The goals of chemotherapy in this context include palliating symptoms, improving health-related quality of life (HRQL), and delaying disease progression.
Midurethral Sling Removal or Revision in Women With Chronic Pain
Authors: Rockefeller Nicholas F. , Petersen Timothy R. , Jeppson Peter C. , Dunivan Gena , Ninivaggio Cara , Meriwether Kate , Gallegos Maxx A. , Komesu Yuko M.
Published: September 2022

(Abstracted from Female Pelvic Med Reconstr Surg 2022;28:e149–e153)

Mesh midurethral slings (MUSs) have been the subject of extensive review and are considered surgically effective for treating stress urinary incontinence with favorable safety profiles. Mesh midurethral slings have known but uncommon complications including mesh exposure, pain, dyspareunia, and infection.
Surgical Complications and Hospital Costs in Robot-Assisted Versus Conventional Laparoscopic Hysterectomy With Concurrent Sacrocolpopexy: Analysis of the Nationwide Readmissions Database
Authors: Andiman Sarah E. , Bui Anthony H. , Ascher-Walsh Charles , Wright Jason D. , Xu Xiao
Published: September 2022

(Abstracted from Female Pelvic Med Reconstr Surg 2022;28:e142–e148)

Uterovaginal prolapse is a common concern that is frequently surgically managed using minimally invasive sacrocolpopexy. This procedure confers a durable mesh graft, while maintaining a low risk of morbidity that is also associated with a shorter hospital stay.
Where Are We in Understanding the Natural History of Polycystic Ovary Syndrome? A Systematic Review of Longitudinal Cohort Studies
Authors: Kiconco Sylvia , Tay Chau Thien , Rassie Kate Louise , Azziz Ricardo , Teede Helena J. , Joham Anju E.
Published: September 2022

(Abstracted from Hum Reprod 2022;37:1255–1273)

Polycystic ovary syndrome (PCOS) is an endocrine-metabolic disorder affecting 5% to 15% of reproductive aged women worldwide. Traditionally, PCOS has been diagnosed based on the presence of 2 of 3 features, including radiologically confirmed polycystic ovaries, oligo/amenorrhea, and hyperandrogenism.
Effects of Pharmacologic Venous Thromboembolism Prophylaxis in Benign Hysterectomy
Authors: Travieso Jennifer , Kamdar Neil , Morgan Daniel M. , As-Sanie Sawsan , Till Sara R.
Published: September 2022

(Abstracted from J Minim Invasive Gynecol 2022;29:776–783)

Venous thromboembolism (VTE) is a potentially preventable perioperative complication of benign hysterectomy, with historic rates of postoperative deep vein thrombosis and pulmonary embolism of 9.6% and 1.8%, respectively. Recent estimates of VTE with routine prophylaxis are lower (0.1% to 0.3% vs 0.24% to 0.6% for laparoscopic and abdominal hysterectomy, respectively).
Low-grade Fibromyxoid Sarcoma With Heterotopic Bone Formation: Case Report and Review of the Literature
Authors: Serinelli Serenella , Mookerjee Gaurav G. , Stock Harlan , de la Roza Gustavo , Damron Timothy , Gitto Lorenzo , Zaccarini Daniel J.
Published: September 2022

Low-grade fibromyxoid sarcoma is an uncommon soft tissue malignant neoplasm with deceptively bland histologic appearance, and a tendency for late recurrence and metastasis. Cases with significant heterotopic ossification are exceedingly rare. In the literature, only 9 cases of low-grade fibromyxoid sarcoma with bone formation proven by histopathology have been described in detail in the literature. We report the case of a 42-year-old male presenting with a 20-year history of a painless tumor in his left upper thigh. Computed tomography images showed coarse punctate central and peripheral calcifications, and the mass was resected. The tumor cells were immunohistochemically positive for MUC4, and also positive for FUS (16p11.2) gene rearrangement by fluorescence in situ hybridization. Besides, immunohistochemistry showed focal weak to moderate staining for TLE-1. At histology, heterotopic ossification was also observed. A diagnosis of low-grade fibromyxoid sarcoma (grade 1, stage T4) was rendered, and prior reports of these tumors with bone formation have not concomitantly described TLE-1 staining. This paper aims to characterize the radiologic, pathologic, and clinical features of low-grade fibromyxoid sarcoma showing heterotopic ossification reported in the literature, and further review the morphologic spectrum of this malignant neoplasm.
The Expression of αvβ3 and Osteopontin in Osteoarthritic Knee Cartilage and Their Correlations With Disease Severity and Chondrocyte Senescence
Authors: Cheng Chao , Tian Jian , Gao Shu-Guang , Zhou Zhi-Hong , Yang Rui-Qi , Xiao Kai , Guo Wei , Liu Li , Yang Hua , Zhang Fang-Jie
Published: September 2022

Osteoarthritis (OA) is the main joint disease associated with aging. Previous studies have confirmed that both osteopontin (OPN) and αvβ3 integrin are involved in the progression of knee OA. The purpose of this study was to determine the expression of OPN and αvβ3 integrin and chondrocyte senescence levels in OA. Forty-six cartilage tissues from normal and knee OA patients were divided into 4 groups of normal, minor, moderate, and severe lesions based on the Mankin score. Immunohistochemistry and western blotting were used to determine the expression of αvβ3, OPN, and senescent-associated-β-galactosidase (SAβ-gal) in articular cartilage. Then, Spearman’s correlation was used to analyze the correlations between the Mankin scores and αvβ3, OPN and SAβ-gal. Pearson correlation analysis was used to analyze the correlations among αvβ3, OPN, and SAβ-gal. The expression of OPN, αvβ3, and SAβ-gal in articular cartilage was explored. αvβ3, OPN, and SAβ-gal proteins were all elevated in OA cartilage, and the correlation coefficient between the Mankin score and the average optical density value of αvβ3, OPN, SAβ-gal were r=0.60, r=0.75, and r=0.87, respectively, all P<0.001; the correlation between the average optical density value of αvβ3 and OPN was r=0.3191, P<0.05; the correlation between αvβ3 and SAβ-gal was r=0.4955, P<0.001; and the correlation between OPN and SAβ-gal was r=0.7821, P<0.001. The correlations among αvβ3, OPN, and SAβ-gal expression in articular cartilage might be important in OA progression and pathogenesis. Nonetheless, more research is needed to elucidate the exact contribution of αvβ3, OPN, and SAβ-gal to the degenerative process of OA.
Ten-year mixed-method evaluation of prelicensure health professional student self-reported learning in an interfaculty pain curriculum
Authors: Dale Craig M. , Cioffi Iacopo , Murphy Laura , Langlois Sylvia , Musa Renata , Stevens Bonnie
Published: September 2022

See commentary: Trouvin A-P. “Ten-year mixed method evaluation of prelicensure health professional student self-reported learning in an interfaculty pain curriculum”: a view on pain education. PAIN Rep 2022;7:e1031.

Introduction:

Student perspectives on interprofessional pain education are lacking.

Objectives:

The purpose of this study was to evaluate ratings of knowledge acquisition and effective presentation methods for prelicensure health professional students attending the University of Toronto Centre for the Study of Pain Interfaculty Pain Curriculum (Canada).

Methods:

A 10-year (2009–2019) retrospective longitudinal mixed-methods approach comprising analysis and integration of quantitative and qualitative data sets was used to evaluate 5 core University of Toronto Centre for the Study of Pain Interfaculty Pain Curriculum learning sessions.

Results:

A total of 10, 693 students were enrolled (2009–2019) with a mean annual attendance of 972 students (±SD:102). The mean proportion of students rating “agree/strongly agree” for knowledge acquisition and effective presentation methods across sessions was 79.3% (±SD:3.4) and 76.7% (±SD:6.0), respectively. Knowledge acquisition or presentation effectiveness scores increased, respectively, over time for 4 core sessions: online self-study pain mechanisms module (P = 0.03/P < 0.001), online self-study opioids module (P = 0.04/P = 0.019), individually selected in-person topical pain sessions (P = 0.03/P < 0.001), and in-person patient or interprofessional panel session (P = 0.03). Qualitative data corroborated rating scores and expanded insight into student expectations for knowledge acquisition to inform real-world clinical practice and interprofessional collaboration; presentation effectiveness corresponded with smaller session size, individually selected sessions, case-based scenarios, embedded knowledge appraisal, and opportunities to meaningfully interact with presenters and peers.

Conclusion:

This study demonstrated positive and increasing prelicensure student ratings of knowledge acquisition and effective presentation methods across multifaceted learning sessions in an interfaculty pain curriculum. This study has implications for pain curriculum design aimed at promoting students' collaborative, patient-centered working skills.
Analysis of Image-Guided Superficial Radiation Therapy (IGSRT) on the Treatment of Early Stage Non-Melanoma Skin Cancer (NMSC) in the Outpatient Dermatology Setting
Authors: Tran Alison , Moloney Mairead , Kaczmarksi Peter , Zheng Songzhu , Desai Alpesh , Desai Tejas , Yu Lio
Published: September 2022

Interest in image-guidance superficial radiation therapy (IGSRT) for the treatment of early-stage Non-Melanoma Skin Cancer (NMSC) has resurfaced given its low complication rates, superior cosmesis and local control and cure rates. Additionally, it has been recommended by the American Academy of Dermatology (AAD) for early-stage NMSC in patients who are considered poor surgical candidates.

Methods

1899 NMSC lesions were treated with energies ranging from 50 to 100 kilovoltage (kV), for a mean of 20.2 fractions, and treatment dose of 5364.4 centigray (cGy). Lesions were treated for a mean of 7.5 weeks and followed for 65.5 weeks. SAS studio was used to conduct Kaplan-Meier analysis to calculate local control rates and account for differences in follow-up intervals. A log-rank test was used to calculate statistical differences between histologies.

Results

Absolute lesion control was achieved in 99.7% of the patients after an average of 7.5 weeks of treatment, with a stable control rate of 99.6% when the follow-up duration was over 12 months.

Conclusion

IGSRT has a high safety profile, can achieve superior cosmesis and should be considered first-line for treating early-stage NMSC tumors as cure rates have been shown to be effective in all NMSC on early follow-up.
The differential regulation of placenta trophoblast bisphosphoglycerate mutase in fetal growth restriction: preclinical study in mice and observational histological study of human placenta
Authors: Stroganov Sima , Harris Talia , Fellus-Alyagor Liat , Moyal Lital Ben , Mayo Romina Plitman , Golani Ofra , Brandis Alexander , Mehlman Tevie , Kovo Michal , Biron-Shental Tal , Dekel Nava , Neeman Michal
Published: September 2022

Background

Fetal growth restriction (FGR) is a pregnancy complication in which a newborn fails to achieve its growth potential, increasing the risk of perinatal morbidity and mortality. Chronic maternal gestational hypoxia, as well as placental insufficiency are associated with increased FGR incidence; however, the molecular mechanisms underlying FGR remain unknown.

Methods

In a case control study of murine and human control and FGR placentae, we implied MR imaging, IHC and metabolomics to assess the levels of BPGM and 2,3 BPG to elucidate the impact of maternal gestational hypoxia, and the molecular mechanisms underlying human FGR.

Results

We show that murine acute and chronic gestational hypoxia recapitulates FGR phenotype and affects placental structure and morphology. Gestational hypoxia decreased labyrinth area, increased the incidence of red blood cells (RBCs) in the labyrinth while expanding the placental spiral arteries (SpA) diameter. Hypoxic placentae exhibited higher hemoglobin-oxygen affinity compared to the control. Placental abundance of bisphosphoglycerate mutase (BPGM) was upregulated in the syncytiotrophoblast and spiral artery trophoblast cells (SpA TGCs) in the murine gestational hypoxia groups compared to the control. In contrast, human FGR placentae exhibited reduced BPGM levels in the syncytiotrophoblast layer compared to placentae from healthy uncomplicated pregnancies. Levels of 2,3 BPG, the product of BPGM, were lower in cord serum of human FGR placentae compared to control. Polar expression of BPGM, was found in both human and mouse placentae syncytiotrophoblast, with higher expression facing the maternal circulation. Moreover, in the murine SpA TGCs expression of BPGM was concentrated exclusively in the apical cell side, in direct proximity to the maternal circulation.

Conclusions

This study suggests a possible involvement of placental BPGM in maternal-fetal oxygen transfer, and in the pathophysiology of FGR.

Funding

This work was supported by the Weizmann - Ichilov (Tel Aviv Sourasky Medical Center) Collaborative Grant in Biomedical Research (to MN) and by the Israel Science Foundation KillCorona grant 3777/19 (to MN, MK).

Graphical abstract
Relative Brain Age Is Associated with Socioeconomic Status and Anxiety/Depression Problems in Youth
Authors: Cohen Jacob W. , Ramphal Bruce , DeSerisy Mariah , Zhao Yihong , Pagliaccio David , Colcombe Stan , Milham Michael P. , Margolis Amy E.
Published: September 2022

Socioeconomic status (SES) has been linked to differences in brain structure and psychiatric risk across the lifespan. Despite many neuropsychiatric disorders emerging in childhood, few studies have examined the influence of SES on brain aging and psychopathology in youth.

We re-analyzed relative brain age (RBA) data from the Healthy Brain Network to examine the influence of SES components (parent education, occupation, household income-to-needs ratio (INR), public assistance enrollment) on RBA. RBA was previously determined using covariation patterns for cortical morphology, white, and subcortical gray matter volumes without SES in predictive models. We also examined associations between RBA and psychiatric symptoms (child behavior checklist). Full case analysis included 470 youth (5-17 years; 61.3% male), self-identifying as White (55%), African American (15%), Hispanic (9%), or multiracial (17.2%). Mean household income was 3.95±2.33 (Mean±SD) times the federal poverty threshold. Multiple linear regression examined if 1) SES components associated with RBA, and 2) RBA associated with psychiatric symptoms. Models covaried for sex, scan location, and parent psychiatric diagnoses.

RBA associated with public assistance (p = 0.03), parent occupation (p = 0.01), and parent psychiatric diagnosis (p = 0.01), but not with INR and parent education. Parent occupation (p = 0.02) and RBA (p = 0.04) associated with CBCL anxiety/depression scores.

Components of SES associated with brain aging, underscoring the risk of omitting these factors in developmental brain research. Further, delayed brain aging was associated with low parental occupational prestige and child anxiety/depression scores, suggesting a possible biological pathway from SES to mental health risk.
The mobilizable plasmid P3 of Salmonella enterica serovar Typhimurium SL1344 depends on the P2 plasmid for conjugative transfer into a broad range of bacteria in vitro and in vivo
Authors: Gaissmaier Marla Sofie , Laganenka Leanid , Herzog Mathias Klaus-Maria , Bakkeren Erik , Hardt Wolf-Dietrich
Published: September 2022

The global rise of drug-resistant bacteria is of great concern. Conjugative transfer of antibiotic resistance plasmids contributes to this antibiotic resistance crisis. Despite the substantial progress in understanding the molecular basis of conjugation in vitro, the in vivo dynamics of intra- and interspecies conjugative plasmid transfer are much less understood. In this study, we focused on the streptomycin resistance-encoding mobilizable plasmid pRSF1010SL1344 (P3) of Salmonella enterica serovar Typhimurium (S. Tm) strain SL1344. We show that P3 is mobilized by interacting with the conjugation machinery of a second, conjugative plasmid pCol1B9SL1344 (P2) of SL1344. Thereby, P3 can be transferred into a broad range of relevant environmental and clinical bacterial isolates in vitro and in vivo. Our data suggests that S. Tm persisters in host tissues can serve as P3 reservoirs and foster transfer of both, P2 and P3 once they reseed the gut lumen. This adds to our understanding of resistance plasmid transfer in ecologically relevant niches including the mammalian gut.

IMPORTANCE

S. Tm is a remarkably adaptable and globally abundant bacterial species that rapidly occupies new niches and survives unstable environmental conditions. As an enteric pathogen, it can potentially interact with a broad range of bacterial species residing in the mammalian gut. High abundance of bacteria in the gut lumen facilitate conjugation and spread of plasmid-encoded antibiotic resistance genes. By studying the transfer dynamics of the P3 plasmid in vitro and in vivo, we illustrate the impact of S. Tm-mediated antibiotic resistance spread via conjugation to a variety of relevant environmental and clinical bacterial isolates. Along with temperate phages or naked DNA, plasmids are among the most critical vehicles driving antibiotic resistance spread. Further understanding of the dynamics and drivers of antibiotic resistance transfer, along with identifying the environmental niches where this occurs, is needed to develop effective solutions for slowing down the emerging threat of multidrug-resistant bacterial pathogens.
RNAlight: a machine learning model to identify nucleotide features determining RNA subcellular localization
Authors: Yuan Guo-Hua , Wang Ying , Wang Guang-Zhong , Yang Li
Published: September 2022

Different RNAs have distinct subcellular localizations. However, nucleotide features that determine these distinct distributions of lncRNAs and mRNAs have yet to be fully addressed. Here, we develop RNAlight, a machine learning model based on LightGBM, to identify nucleotide k-mers contributing to the subcellular localizations of mRNAs and lncRNAs. With the Tree SHAP algorithm, RNAlight extracts nucleotide features for cytoplasmic or nuclear localization of RNAs, indicating the sequence basis for distinct RNA subcellular localizations. By assembling k-mers to sequence features and subsequently mapping to known RBP-associated motifs, different types of sequence features and their associated RBPs were additionally uncovered for lncRNAs and mRNAs with distinct subcellular localizations. Finally, we extended RNAlight to precisely predict the subcellular localizations of other types of RNAs, including snRNAs, snoRNAs and different circular RNA transcripts, suggesting the generality of using RNAlight for RNA subcellular localization prediction.

Key points

A machine learning model, RNAlight, is developed to efficiently and sensitively predict subcellular localizations of mRNAs and lncRNAs.

With embedded Tree SHAP algorithm, RNAlight further reveals distinct key sequence features and their associated RBPs for subcellular localizations of mRNAs or lncRNAs.

RNAlight is successfully extended for the subcellular localization prediction of additional types of noncoding RNAs that were not used for model development, such as circular RNAs, suggesting its generality in RNA subcellular localization prediction.

RNAlight is freely available at https://github.com/YangLab/RNAlight.
HuntingDrosophilaviruses from wild populations: a novel isolation approach and characterization of viruses
Authors: Bruner-Montero Gaspar , Luque Carlos , Ding Shuai Dominique , Day Jonathan P. , Jiggins Francis M.
Published: September 2022

Metagenomic studies have demonstrated that viruses are extremely diverse and abundant in insects, but the difficulty of isolating them means little is known about the biology of these newly discovered viruses. To overcome this challenge inDrosophila, we created a cell line with increased susceptibility to infection and detected novel viruses by the presence of double-stranded RNA. We demonstrate the utility of these tools by isolating La Jolla virus (LJV) and Newfield virus (NFV) from several wildDrosophilapopulations. These viruses have different potential host ranges, with distinct abilities to replicate in fiveDrosophilaspecies. Similarly, in some species they cause high mortality and in others they are comparatively benign. In three species, NFV but not LJV caused large declines in female fecundity. This sterilization effect was associated with differences in tissue tropism, as NFV but not LJV was able to infectDrosophila melanogasterovaries. We saw a similar effect in the invasive pest of fruit cropsDrosophila suzukii, where oral infection with NFV caused reductions in the fecundity, suggesting it has potential as a biocontrol agent. In conclusion, a simple protocol allowed us to isolate new viruses and demonstrate that viruses identified by metagenomics have a large effect on the fitness of the model organismD. melanogasterand related species.
Distinct brain networks for remote episodic memory depending on content and emotional value
Authors: Auguste Anne , Fourcaud-Trocmé Nicolas , Meunier David , Gros Alexandra , Garcia Samuel , Messaoudi Belkacem , Thevenet Marc , Ravel Nadine , Veyrac Alexandra
Published: September 2022

The mechanisms that underlie the storage of old nontraumatic episodic memories remain enigmatic because of the difficulty in modelling this particular type of memory in humans and animals. Episodic memories combine incidental and occasional “What-Where-When/In which context” multisensory information and can be stored for long periods of time. Here, using a task in rodents that models human episodic memory, including odour/place/context components, we applied advanced behavioural and computational analyses and brain imaging of c-Fos and Zif268 to characterize remote episodic memories and their engrams for the first time. We show that the content and accuracy of memories vary across individuals and depend on the emotional relationship with odours experienced during episodes. Activated brain networks reflect the nature and content of remote episodic memories and their transformation over time, and emotional cortico-hippocampal networks play critical roles in maintaining vivid memories.
A T1R-independent mechanism for responses to hyperosmotic sugars involves a carbonic anhydrase-sensitive mechanism in Type III receptor cells
Authors: Kalyanasundar B. , Blonde Ginger D. , Spector Alan C. , Travers Susan P.
Published: September 2022

Recent findings from our laboratory demonstrated that the rostral nucleus of solitary tract (rNST) retains some responsiveness to glutamate (MSG+amiloride-MSGa) and sugars in mice lacking the canonical T1R receptors for these tastants. Here, we recorded from the parabrachial nucleus (PBN) in mice lacking the T1R1+T1R3 heterodimer (KO1+3), using warm stimuli to optimize sugar responses and employing extended concentrations and pharmacological agents to probe mechanisms. MSGa+IMP responses were not synergized in KO1+3 mice but responses to MSGa were similar to those in B6 (WT) mice. Glutamate responses in the neurons tested were unaffected by topical application of an mGluR4 antagonist. PBN T1R-independent sugar responses, including those to concentrated glucose, were more evident than in rNST. Sugar responses were undiminished by phlorizin, an inhibitor of SGLT, a component of a hypothesized alternative glucose-sensing mechanism. There were no sugar/umami “best” neurons in KO1+3 mice, and instead, sugars activated cells that displayed acid and amiloride-insensitive NaCl responses. In WTs, concentrated sugars activated “sugar/umami” cells but also electrolyte-sensitive neurons. The efficacy of hyperosmotic sugars for driving neurons broadly responsive to electrolytes implied an origin from Type III taste bud cells. To test this, we used the carbonic anhydrase (CA) inhibitor dorzolamide (DRZ), previously shown to inhibit amiloride-insensitive sodium responses arising from Type III cells. Dorzolamide had no effect on sugarelicited responses in WT sugar/umami PBN neurons but strongly suppressed them in WT and KO electrolyte-generalist neurons. These findings suggest a novel T1R-independent mechanism for hyperosmotic sugars, involving a CA-dependent mechanism in Type-III taste bud cells.

Significance Statement

Since the discovery of theTas1rgene family that encodes receptors that lead to sweet and umami taste perception two decades ago, evidence has accrued that mice lacking these receptors maintain some degree of behavioral, physiological, and neural responsiveness to sugars and monosodium glutamate. But the basis for the remaining sensitivity to these nutritionally relevant compounds has remained elusive. Here we recorded from parabrachial nucleus taste neurons. Glutamate responses in mice lacking T1R1+T1R3 were unaffected by oral treatment of mGluR4 receptor antagonist suggesting that some T1R-independent glutamate responses are mediated by a different transduction pathway. Moreover, we identified a novel basis for T1R-independent responsiveness to hyperosmotic sugars that relies on carbonic anhydrase-mediated mechanism found in Type III taste bud cells.
To be and not to be: Wide-field Ca2+imaging reveals neocortical functional segmentation combines stability and flexibility
Authors: Nietz Angela K. , Streng Martha L. , Popa Laurentiu S. , Carter Russell E. , Flaherty Evelyn , Aronson Justin D. , Ebner Timothy J.
Published: September 2022

The stability and flexibility of the functional parcellation of the cerebral cortex is fundamental to how familiar and novel information is both represented and stored. We leveraged new advances in Ca2+sensors and microscopy to understand the dynamics of functional segmentation in the dorsal cerebral cortex. We performed wide-field Ca2+imaging in head-fixed mice and used spatial Independent Component Analysis (ICA) to identify independent spatial sources of Ca2+fluorescence. The imaging data were evaluated over multiple timescales and discrete behaviors including resting, walking, and grooming. When evaluated over the entire dataset, a set of template independent components (ICs) were identified that were common across behaviors. Template ICs were present across a range of timescales, from days to 30 seconds, although with lower occurrence probability at shorter timescales, highlighting the stability of the functional segmentation. Importantly, unique ICs emerged at the shorter duration timescales that could act to transiently refine the cortical network. When data were evaluated by behavior, both common and behavior-specific ICs emerged. Each behavior is composed of unique combinations of common and behavior-specific ICs. These observations suggest that cerebral cortical functional segmentation exhibits considerable spatial stability over time and behaviors while retaining the flexibility for task-dependent reorganization.
Development of a 5-FU Modified miR-129 Mimic as a Therapeutic for Non-Small Cell Lung Cancer
Authors: Hwang Ga-Ram , Yuen John G. , Fesler Andrew , Farley Hannah , Haley John D. , Ju Jingfang
Published: September 2022

Lung cancer is the leading cause of cancer-related deaths in the United States with non-small cell lung cancer (NSCLC) accounting for most cases. Despite advances in cancer therapeutics, the 5-year survival rate has remained poor due to several contributing factors, including its resistance to therapeutics. Therefore, there is a pressing need to develop therapeutics that can overcome resistance. Non-coding RNAs, including microRNAs (miRNAs), have been found to contribute to cancer resistance and therapeutics by modulating the expression of several targets involving multiple key mechanisms. In this study, we investigated the therapeutic potential of miR-129 modified with 5-fluorouracil (5-FU) in NSCLC. Our results show that 5-FU modified miR-129 (5-FU-miR-129) inhibits proliferation, induces apoptosis, and retains function as a miRNA in NSCLC cell lines A549 and Calu-1. Notably, we observed that 5-FU-miR-129 was able to overcome resistance to tyrosine kinase inhibitors and chemotherapy in cell lines resistant to erlotinib or 5-FU. Furthermore, we observed that the inhibitory effect of 5-FU-miR-129 can also be achieved in NSCLC cells under vehicle-free conditions. Finally, 5-FU-miR-129 inhibited NSCLC tumor growth and extended survivalin vivowithout toxic side effects. Altogether, our results demonstrate the potential of 5-FU-miR-129 as a highly potent cancer therapeutic in NSCLC.
Development of the First High-Density Linkage Map in the Maize Weevil, Sitophilus zeamais
Authors: Baltzegar Jennifer Fountain , Gould Fred L.
Published: September 2022

The maize weevil, Sitophilus zeamais, is a worldwide pest that disproportionately affects subsistence farmers in developing countries. Damage from this pest threatens food security in these communities as widely available and effective control methods are lacking. With advances over the last decade in the development of advanced genetic pest management techniques, addressing pest issues at the ecosystem level as opposed to the farm level may be a possibility. However, pest species selected for genetic management techniques require a well-characterized genome and few genomic tools have been developed for maize weevil. Here, we have measured the genome size and developed the first genetic linkage map for this species. The genome size was determined using flow cytometry as 682 Mb and 674 Mb for females and males, respectively. The linkage map contains 11 linkage groups, which correspond to the 10 autosomes and 1 X-chromosome found in the species and it contains 1,121 SNPs. This linkage map will be useful for assembling a complete genome for maize weevil.
The histone chaperone NASP maintains H3-H4 reservoirs in the early Drosophila embryo
Authors: Tirgar Reyhaneh , Davies Jonathan P. , Plate Lars , Nordman Jared T.
Published: September 2022

Histones are essential for chromatin packaging and histone supply must be tightly regulated as excess histones are toxic. To drive the rapid cell cycles of the early embryo, however, excess histones are maternally deposited. Therefore, soluble histones must be buffered by histone chaperones but the chaperone necessary to stabilize soluble H3-H4 pools in the Drosophila embryo has yet to be identified. Here, we show that CG8223, the Drosophila ortholog of NASP, is a H3-H4-specific chaperone in the early embryo. NASP specifically binds to H3-H4 in the early embryo. We demonstrate that, while a NASP null mutant is viable in Drosophila, NASP is maternal effect lethal gene. Embryos laid by NASP mutant mothers have a reduce rate of hatching and show defects in early embryogenesis. Critically, soluble H3-H4 pools are degraded in embryos laid by NASP mutant mothers. Our work identifies NASP as the critical H3-H4 histone chaperone in the Drosophila embryo.