University Administrators’ Visions for the Recovery of International Student Exchange in a Post–COVID-19 World

Objectives: Little is known about how international functions of higher education, such as exchange programmes, can be resumed during recovery from a disruptive global crisis, such as COVID-19. We collected the opinions of administrators of international exchange programmes regarding their plans to resume their exchange programmes in the recovery phase and identified variations in the responses concerning institution type (public vs. private) and the presence or absence of a medical school. Method: We used multiple-choice survey questions in our study, resulting in 180 valid responses. We examined overall patterns using descriptive statistics and institutional uniqueness using Fisher’s exact test. Results: Governing organisations and domestic university networks are expected to initiate the resumption of student exchange programmes. Respondents indicate that they would rely on infection prevention experts at their institutions as sources of information for their decision-making. Public universities would rely more extensively on their staff’s opinions whilst private universities would consult with external experts. Universities with a medical school indicated a greater likelihood of referring to the opinions of experts at their institutions. Implication for Theory and/or Practice: Higher education systems vary across nations. However, extant studies have shown some shared features, and the findings may have implications for higher education institutions internationally. Policy incentives and support may encourage public universities to participate in the global recovery of international education. During global public health infectious crises, institutions without a medical school may require more government support. Conclusions: Institutional variations should be considered to effectively encourage universities to adapt to changing dynamics in the recovery of international education. Method: The study used multiple-choice survey questions, resulting in 180 valid responses. The study examined overall patterns using descriptive statistics and institutional uniqueness using Fisher\u27s exact test. Results: Governing organisations and domestic university networks are expected to initiate the resumption of student exchange. Respondents indicate that they would rely on infection prevention experts at their institutions as sources of information for their decision-making. Public universities would rely more extensively on their staff’s opinions whilst private universities would consult with external experts. Universities with a medical school indicated a greater likelihood of referring to the opinions of experts at their institutions. Implication for Theory and/or Practice: The higher education systems vary across nations. However, extant studies have shown some shared features, and the findings may have implications for higher education institutions internationally. Policy incentives and support may encourage public universities to participate in the global recovery of international education. During global public health infectious crises, institutions without a medical school may require more government support. Conclusions: Institutional variations should be considered to effectively encourage universities to adapt to changing dynamics in the recovery of international education

The clinical impact of macrophage polarity after Kasai portoenterostomy in biliary atresia

IntroductionBiliary atresia (BA) is a cholestatic hepatopathy caused by fibrosing destruction of intrahepatic and extrahepatic bile ducts, and its etiology has not been clearly revealed. In BA, liver fibrosis progression is often observed even after Kasai portoenterostomy (KPE), and more than half of cases require liver transplantation in their lifetime in Japan. Macrophages play an important role in liver fibrosis progression and are classically divided into proinflammatory (M1) and fibrotic macrophages (M2), whose phenotypic transformation is called “macrophage polarity.” The polarity has been reported to reflect the tissue microenvironment. In this study, we examined the relationship between macrophage polarity and the post-KPE clinical course.Materials and methodsThirty BA patients who underwent KPE in our institution from 2000 to 2020 were recruited. Multiple immunostainings for CD68, CD163, CK19, and α-SMA were carried out on liver biopsy specimens obtained at KPE. ROC curves were calculated based on each clinical event, and the correlation with the clinical data was analyzed.Results and discussionThe M2 ratio, defined as the proportion of M2 macrophages (CD163-positive cells), was correlated inversely with the occurrence of postoperative cholangitis (AUC: 0.7602). The patients were classified into M2 high (n = 19) and non-high (n = 11) groups based on an M2 ratio value obtained from the Youden index ( = 0.918). As a result, pathological evaluations (Metavir score, αSMA area fraction, and CK19 area fraction) were not significantly different between these groups. In mild liver fibrosis cases (Metavir score = 0–2), the M2 non-high group had a significantly lower native liver survival rate than the high group (p = 0.02). Moreover, 4 out of 8 cases in the M2 non-high group underwent early liver transplantation within 2 years after KPE.ConclusionsNon-M2 macrophages, including M1 macrophages, may be correlated with postoperative cholangitis, and the M2 non-high group in mild liver fibrosis cases had a significantly lower native liver survival rate than the high group, requiring early liver transplantation in this study. Preventing advanced liver fibrosis is a key factor in improving native liver survival for BA patients, and liver macrophages may play important roles in liver homeostasis and the promotion of inflammation and fibrosis

LimF is a versatile prenyltransferase catalyzing histidine-C-geranylation on diverse nonnatural substrates

Prenylation plays an important role in diversifying structure and function of secondary metabolites. Although several cyanobactin prenyltransferases have been characterized, their modes of action are mainly limited to the modification of electron-rich hetero atoms. Here we report a unique prenyltransferase originating from Limnothrix sp. CACIAM 69d, referred to as LimF, which catalyzes an unprecedented His-C-geranylation. Interestingly, LimF executes the geranylation on not only its native peptide substrate but also a wide range of exotic peptides, including thioether-closed macrocycles. We have also serendipitously uncovered an ability of Tyr-O-geranylation as the secondary function of LimF, indicating it is an unusual bifunctional prenyltransferase. Crystallographic analysis of LimF complexed with a pentapeptide substrate and a prenyl donor analog provides structural basis for its unique His recognition and its bifunctionality. Lastly, we show the LimF’s prenylation ability on various bioactive molecules containing an imidazole group, highlighting its potential as a versatile biocatalyst for site-specific geranylation

A Compact Reprogrammed Genetic Code for De Novo Discovery of Proteolytically Stable Thiopeptides

Thiopeptides make up a group of structurally complex peptidic natural products holding promise in bioengineering applications. The previously established thiopeptide/mRNA display platform enables de novo discovery of natural product-like thiopeptides with designed bioactivities. However, in contrast to natural thiopeptides, the discovered structures are composed predominantly of proteinogenic amino acids, which results in low metabolic stability in many cases. Here, we redevelop the platform and demonstrate that the utilization of compact reprogrammed genetic codes in mRNA display libraries can lead to the discovery of thiopeptides predominantly composed of nonproteinogenic structural elements. We demonstrate the feasibility of our designs by conducting affinity selections against Traf2- and NCK-interacting kinase (TNIK). The experiment identified a series of thiopeptides with high affinity to the target protein (the best KD = 2.1 nM) and kinase inhibitory activity (the best IC50 = 0.15 μM). The discovered compounds, which bore as many as 15 nonproteinogenic amino acids in an 18-residue macrocycle, demonstrated high metabolic stability in human serum with a half-life of up to 99 h. An X-ray cocrystal structure of TNIK in complex with a discovered thiopeptide revealed how nonproteinogenic building blocks facilitate the target engagement and orchestrate the folding of the thiopeptide into a noncanonical conformation. Altogether, the established platform takes a step toward the discovery of thiopeptides with high metabolic stability for early drug discovery applications

A Compact Reprogrammed Genetic Code for De Novo Discovery of Proteolytically Stable Thiopeptides

Thiopeptides make up a group of structurally complex peptidic natural products holding promise in bioengineering applications. The previously established thiopeptide/mRNA display platform enables de novo discovery of natural product-like thiopeptides with designed bioactivities. However, in contrast to natural thiopeptides, the discovered structures are composed predominantly of proteinogenic amino acids, which results in low metabolic stability in many cases. Here, we redevelop the platform and demonstrate that the utilization of compact reprogrammed genetic codes in mRNA display libraries can lead to the discovery of thiopeptides predominantly composed of nonproteinogenic structural elements. We demonstrate the feasibility of our designs by conducting affinity selections against Traf2- and NCK-interacting kinase (TNIK). The experiment identified a series of thiopeptides with high affinity to the target protein (the best KD = 2.1 nM) and kinase inhibitory activity (the best IC50 = 0.15 μM). The discovered compounds, which bore as many as 15 nonproteinogenic amino acids in an 18-residue macrocycle, demonstrated high metabolic stability in human serum with a half-life of up to 99 h. An X-ray cocrystal structure of TNIK in complex with a discovered thiopeptide revealed how nonproteinogenic building blocks facilitate the target engagement and orchestrate the folding of the thiopeptide into a noncanonical conformation. Altogether, the established platform takes a step toward the discovery of thiopeptides with high metabolic stability for early drug discovery applications

Successful multidisciplinary treatment for synchronous advanced esophageal and cecal cancers after total gastrectomy with reconstruction by jejunal interposition

Abstract Background Esophageal squamous cell carcinoma is characterized by field cancerization, wherein multiple cancers occur in the esophagus, head and neck, and stomach. Synchronous esophageal and colorectal cancers are also encountered with a certain frequency. A good prognosis can be expected if the tumors in both locations can be safely and completely removed. For patients with multiple cancers that occur simultaneously with esophageal cancer, it is necessary to perform a staged operation, taking into consideration the associated surgical invasiveness. It is also necessary to select multidisciplinary treatment depending on the degree of progression of the multiple lesions. We report our rare experience with a staged operation for a patient with synchronous advanced cancers of the esophagus and cecum who had previously undergone total gastrectomy with reconstruction by jejunal interposition for gastric cancer. Case presentation A 71-year-old man with a history of reconstruction by jejunal interposition after total gastrectomy was diagnosed as having multiple synchronous esophageal and cecal cancers. After neoadjuvant chemotherapy, we performed a planned two-stage operation, with esophagectomy and jejunostomy in the first stage and ileocecal resection and jejunal reconstruction with vascular anastomosis in the second. Postoperatively, the patient was relieved without major complications, and both tumors were amenable to curative pathologic resection. Conclusions Our procedure reported here may be recommended as an option for staged resection and reconstruction in patients with simultaneous advanced esophageal and cecal cancer after total gastrectomy

Oligometastases of Esophageal Squamous Cell Carcinoma: A Review

Patients with oligometastases show distant relapse in only a limited number of regions. Local therapy such as surgical resection, radiotherapy, chemoradiotherapy, and radiofrequency ablation for the relapsed sites may thus improve patient survival. Oligometastases are divided into oligo-recurrence and sync-oligometastases. Oligo-recurrence indicates a primary lesion that is controlled, and sync-oligometastases indicate a primary lesion that is not controlled. The management of oligo-recurrence and sync-oligometastases in esophageal squamous cell carcinoma has not been clearly established, and treatment outcomes remain equivocal. We reviewed 14 articles, including three phase II trials, that were limited to squamous cell carcinoma. Multimodal treatment combining surgical resection and chemoradiotherapy for oligo-recurrence of esophageal squamous cell carcinoma appears to be a promising treatment. With the development of more effective chemotherapy and regimens that combine immune checkpoint inhibitors, it will become more likely that sync-oligometastases that were unresectable at the initial diagnosis can be brought to conversion surgery. Currently, a randomized, controlled phase III trial is being conducted in Japan to compare a strategy for performing definitive chemoradiotherapy and, if necessary, salvage surgery with a strategy for conversion surgery in patients who can be resected by induction chemotherapy

低血糖発作を繰り返す反応性低血糖症症例の2度の妊娠管理に関する報告

雑誌掲載版耐糖能異常合併妊娠では妊娠中の厳格な血糖コントロールにおいて、血糖値の目標下限値は70mg/dlとされているが、低血糖が母児へ与える影響については不明な点が多い。動物実験では妊娠初期の低血糖が胎児奇形や発育遅滞に影響するといった報告もある。今回われわれは、非妊娠時より低血糖発作を繰り返した症例で、2度の妊娠管理を経験した。症例は19歳ごろより空腹時の脱力感を自覚し、21歳で随時血糖値24mg/dlの低血糖発作を発見され、2007年1月当科紹介初診。低血糖の入院精査にて、インスリノーマや内分泌疾患などは否定し、75gブドウ糖負荷試験(OGTT)にて血糖値は0分値65mg/dl、60分値122mg/dl、120分値65mg/dlであり、インスリン値からも反応性低血糖症と診断した。αグルコシダーゼ阻害薬を開始したが、挙児希望のため内服を中止し、2007年10月(22歳)に第1子の妊娠判明。妊娠19週2日に食後血糖値66mg/dl、HbA1c 4.6%、40〜50mg/dlの低血糖発作を繰り返しており、補食や分割食で対応していた。妊娠25週5日の75g OGTTでは0分値78mg/dl、60分値154mg/dl、120分値112mg/dl。5分割食として低血糖発作を予防し、妊娠40週1日で2420g、低出生体重児でSFD(small for date)の女児を出産。25歳時には第2子の妊娠判明、HbA1c 5.4%であり、妊娠初期から5分割食を指示し、重篤な低血糖発作はなく経過。妊娠37週4日で2754g、AFD(appropriate for date)の女児を出産。母体体重は第1子妊娠中には約11kg、第2子妊娠中には約8kgの増加であった。2児ともに奇形や明らかな新生児合併症はなく、その後の発育も順調である。本症例では、胎児発育に影響を与えるその他の要因を認めず、2回の異なる妊娠経過から、妊娠中の繰り返す低血糖は児の発育遅延に関係する可能性が考えられた